A species of hydatid tapeworm (class CESTODA) in the family Taeniidae, whose adult form infects the DIGESTIVE TRACT of DOGS, other canines, and CATS. The larval form infects SHEEP; PIGS; HORSES; and may infect humans, where it migrates to various organs and forms permanent HYDATID CYSTS.
Substances that are recognized by the immune system and induce an immune reaction.
A genus of very small TAPEWORMS, in the family Taeniidae. The adult form is found in various CARNIVORA but not humans. The larval form is seen in humans under certain epidemiologic circumstances.
An infection caused by the infestation of the larval form of tapeworms of the genus Echinococcus. The liver, lungs, and kidney are the most common areas of infestation.
Substances elaborated by bacteria that have antigenic activity.
A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*44 allele family.
Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.
Immunoglobulins produced in a response to HELMINTH ANTIGENS.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
A subclass of segmented worms comprising the tapeworms.
Liquid material found in epithelial-lined closed cavities or sacs.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.
Substances elaborated by viruses that have antigenic activity.
The larval form of various tapeworms of the genus Taenia.
A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*27 allele family.
A classification of B-lymphocytes based on structurally or functionally different populations of cells.
Antibodies produced by a single clone of cells.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Proteins found in any species of helminth.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
A bacterium which is one of the etiologic agents of bacillary dysentery (DYSENTERY, BACILLARY) and sometimes of infantile gastroenteritis.
Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.
Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
An encapsulated lymphatic organ through which venous blood filters.
Substances of fungal origin that have antigenic activity.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
The major group of transplantation antigens in the mouse.
Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.
Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
The activated center of a lymphoid follicle in secondary lymphoid tissue where B-LYMPHOCYTES are stimulated by antigens and helper T cells (T-LYMPHOCYTES, HELPER-INDUCER) are stimulated to generate memory cells.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.
Proteins found in any species of bacterium.
A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.
Sites on an antigen that interact with specific antibodies.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.
An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B LYMPHOCYTES.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Established cell cultures that have the potential to propagate indefinitely.
Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
T-cell enhancement of the B-cell response to thymic-dependent antigens.
A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.
The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, CD15 antigen is a stage-specific embryonic antigen.
Antigens which may directly stimulate B lymphocytes without the cooperation of T lymphocytes.
A component of the B-cell antigen receptor that is involved in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. It is expressed almost exclusively in B-LYMPHOCYTES and serves as a useful marker for B-cell NEOPLASMS.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.
Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.
Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies.
A member of the tumor necrosis factor receptor superfamily found on most T-LYMPHOCYTES. Activation of the receptor by CD70 ANTIGEN results in the increased proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A tumor necrosis factor superfamily member that plays a role in the regulation of B-LYMPHOCYTE survival. It occurs as a membrane-bound protein that is cleaved to release an biologically active soluble form with specificity to TRANSMEMBRANE ACTIVATOR AND CAML INTERACTOR PROTEIN; B-CELL ACTIVATION FACTOR RECEPTOR; and B-CELL MATURATION ANTIGEN.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Human immune-response or Class II antigens found mainly, but not exclusively, on B-lymphocytes and produced from genes of the HLA-D locus. They are extremely polymorphic families of glycopeptides, each consisting of two chains, alpha and beta. This group of antigens includes the -DR, -DQ and -DP designations, of which HLA-DR is most studied; some of these glycoproteins are associated with certain diseases, possibly of immune etiology.
Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.
Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Lymphocyte progenitor cells that are restricted in their differentiation potential to the B lymphocyte lineage. The pro-B cell stage of B lymphocyte development precedes the pre-B cell stage.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).
Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.
Ordered rearrangement of B-lymphocyte variable gene regions coding for the IMMUNOGLOBULIN CHAINS, thereby contributing to antibody diversity. It occurs during the differentiation of the IMMATURE B-LYMPHOCYTES.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
A lectin and cell adhesion molecule found in B-LYMPHOCYTES. It interacts with SIALIC ACIDS and mediates signaling from B-CELL ANTIGEN RECEPTORS.
Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.
Glycoproteins found on the membrane or surface of cells.
Cells of the lymphoid series that can react with antigen to produce specific cell products called antibodies. Various cell subpopulations, often B-lymphocytes, can be defined, based on the different classes of immunoglobulins that they synthesize.
Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
Antigenic determinants recognized and bound by the B-cell receptor. Epitopes recognized by the B-cell receptor are located on the surface of the antigen.
Antigens of the virion of the HEPATITIS B VIRUS or the Dane particle, its surface (HEPATITIS B SURFACE ANTIGENS), core (HEPATITIS B CORE ANTIGENS), and other associated antigens, including the HEPATITIS B E ANTIGENS.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
A member of the tumor necrosis factor receptor superfamily that specifically binds B-CELL ACTIVATING FACTOR. It is found on B-LYMPHOCYTES and plays a role in maturation and survival of B-cells. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
The class of heavy chains found in IMMUNOGLOBULIN M. They have a molecular weight of approximately 72 kDa and they contain about 57 amino acid residues arranged in five domains and have more oligosaccharide branches and a higher carbohydrate content than the heavy chains of IMMUNOGLOBULIN G.
Ordered rearrangement of B-lymphocyte variable gene regions of the IMMUNOGLOBULIN HEAVY CHAINS, thereby contributing to antibody diversity. It occurs during the first stage of differentiation of the IMMATURE B-LYMPHOCYTES.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.
Antigens associated with specific proteins of the human adult T-cell immunodeficiency virus (HIV); also called HTLV-III-associated and lymphadenopathy-associated virus (LAV) antigens.
Immunoglobulins produced in response to VIRAL ANTIGENS.
One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
CXCR receptors isolated initially from BURKITT LYMPHOMA cells. CXCR5 receptors are expressed on mature, recirculating B-LYMPHOCYTES and are specific for CHEMOKINE CXCL13.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Ordered rearrangement of B-lymphocyte variable gene regions coding for the kappa or lambda IMMUNOGLOBULIN LIGHT CHAINS, thereby contributing to antibody diversity. It occurs during the second stage of differentiation of the IMMATURE B-LYMPHOCYTES.
Antigens stimulating the formation of, or combining with heterophile antibodies. They are cross-reacting antigens found in phylogenetically unrelated species.
A programmed mutation process whereby changes are introduced to the nucleotide sequence of immunoglobulin gene DNA during development.
Proteins prepared by recombinant DNA technology.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.
Benzene derivatives which are substituted with three nitro groups in any position.
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
The sum of the weight of all the atoms in a molecule.
The number of LYMPHOCYTES per unit volume of BLOOD.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.
The hepatitis B antigen within the core of the Dane particle, the infectious hepatitis virion.
T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.
Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.
Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.
A method to identify and enumerate cells that are synthesizing ANTIBODIES against ANTIGENS or HAPTENS conjugated to sheep RED BLOOD CELLS. The sheep red blood cells surrounding cells secreting antibody are lysed by added COMPLEMENT producing a clear zone of HEMOLYSIS. (From Illustrated Dictionary of Immunology, 3rd ed)
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional DENDRITIC CELLS associated with T-CELLS. They are derived from MESENCHYMAL STEM CELLS and are negative for class II MHC antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have FC RECEPTORS and C3B RECEPTORS that hold antigen in the form of ANTIGEN-ANTIBODY COMPLEXES on their surfaces for long periods for recognition by B-CELLS.
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.
An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.
Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.
A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.
A sex-specific cell surface antigen produced by the sex-determining gene of the Y chromosome in mammals. It causes syngeneic grafts from males to females to be rejected and interacts with somatic elements of the embryologic undifferentiated gonad to produce testicular organogenesis.
A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.
Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Elements of limited time intervals, contributing to particular results or situations.
One of the types of light chain subunits of the immunoglobulins with a molecular weight of approximately 22 kDa.
An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A glycolipid, cross-species antigen that induces production of antisheep hemolysin. It is present on the tissue cells of many species but absent in humans. It is found in many infectious agents.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).
Immunoglobulins produced in a response to PROTOZOAN ANTIGENS.
A CXC chemokine that is chemotactic for B-LYMPHOCYTES. It has specificity for CXCR5 RECEPTORS.
A general term for various neoplastic diseases of the lymphoid tissue.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
A major histocompatibily complex class I-like protein that plays a unique role in the presentation of lipid ANTIGENS to NATURAL KILLER T-CELLS.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.

BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells. (1/2715)

Signaling through the B cell receptor (BCR) is essential for B cell function and development. Despite the key role of Syk in BCR signaling, little is known about the mechanism by which Syk transmits downstream effectors. BLNK (B cell LiNKer protein), a substrate for Syk, is now shown to be essential in activating phospholipase C (PLC)gamma 2 and JNK. The BCR-induced PLC gamma 2 activation, but not the JNK activation, was restored by introduction of PLC gamma 2 membrane-associated form into BLNK-deficient B cells. As JNK activation requires both Rac1 and PLC gamma 2, our results suggest that BLNK regulates the Rac1-JNK pathway, in addition to modulating PLC gamma 2 localization.  (+info)

Rel-dependent induction of A1 transcription is required to protect B cells from antigen receptor ligation-induced apoptosis. (2/2715)

In response to different extracellular signals, Rel/NF-kappaB transcription factors are critical regulators of apoptosis in a variety of cell types. Here we show that in normal B and T cells, expression of the Bcl-2 prosurvival homolog, A1, is rapidly induced in a Rel-dependent manner by mitogens. In B-cell lines derived from c-rel-/- mice, which like primary cells lacking Rel undergo apoptosis in response to antigen receptor ligation, constitutive expression of an A1 transgene inhibits this pathway to cell death. These findings are the first to show that Rel/NF-kappaB regulates physiologically the expression of a Bcl-2-like protein that is critical for the control of cell survival during lymphocyte activation.  (+info)

Interaction of B cells with activated T cells reduces the threshold for CD40-mediated B cell activation. (3/2715)

CD154-CD40 interactions are of central importance for the induction of antibody responses to T-dependent antigens. Since most anti-CD40 mAb are only weak B cell mitogens, it is believed that under physiological conditions, signals through CD40 synergize with those from other receptors on B cells to induce B cell activation. We show here that the interaction of either normal B cells, or those from CBA/N (xid) mice, with CD3-activated primary T cells in whole spleen cell cultures markedly reduces the threshold for B cell activation via CD40. Hence, these pre-activated cells undergo vigorous proliferation when stimulated with either optimal or suboptimal concentrations of weakly mitogenic anti-CD40 mAb, or with soluble CD40 ligand. Blocking experiments indicate that the establishment of this priming effect requires stimulation via CD40 itself, plus T cell-derived IL-2. In support of this concept, only CD3/CD28-pre-activated, but not CD3-pre-activated T cells induce this effect, unless the co-cultures of B cells with the latter T cells are supplemented with IL-2. Although B cells activated in this fashion do express higher levels of CD40 than naive cells, we believe that this is insufficient to explain the observed dramatic effects on their proliferative capacity. Rather we propose that T cell-dependent B cell activation induces fundamental changes in the signalling machinery invoked by ligation of CD40. It is likely that this amplification loop could play an important role during the initiation of antibody responses to T-dependent antigens, when activated CD4 T cells only express low levels of CD154.  (+info)

Induction of human immunoglobulin synthesis and secretion in somatic cell hybrids of mouse myeloma and human B lymphocytes from patients with agammaglobulinemia. (4/2715)

Somatic cell hybrid clones were isolated from the fusion of RPC 5,4 mouse myeloma cells and B lymphocytes from three patients with agammaglobulinemia. One patient had X-linked agammaglobulinemia; the remaining two patients had common varied agammaglobulinemia. All three patients had B lymphocytes which fail to secrete immunoglobulin. The hybrid nature of the clones was established by examination of metaphase chromosome spreads. Most of the clones from all three patients expressed surface immunoglobulin of mouse and human parental origin. Clones from two of the patients had fewer cells with surface Ig than hybrids from normal persons, while clones from the third patient had large numbers of surface Ig fluorescent cells. Most of the clones from all three patients synthesized and secreted human and mouse immunoglobulin. As determined by sodium dodecyl sulfate acrylamide gel electrophoresis of radioactively labeled proteins, clones from each of the patients produced human gamma, alpha, and mu-heavy chains. These studies demonstrate the presence of functional structural genes coding for human immunoglobulin heavy chains in B lymphocytes of patients with agammaglobulinemia. Further, they represent induction in the somatic cell hybrids of a gene product not expressed in the parental B lymphocytes.  (+info)

Encoding of Ca2+ signals by differential expression of IP3 receptor subtypes. (5/2715)

Inositol 1,4,5-trisphosphate (IP3) plays a key role in Ca2+ signalling, which exhibits a variety of spatio-temporal patterns that control important cell functions. Multiple subtypes of IP3 receptors (IP3R-1, -2 and -3) are expressed in a tissue- and development-specific manner and form heterotetrameric channels through which stored Ca2+ is released, but the physiological significance of the differential expression of IP3R subtypes is not known. We have studied the Ca2+-signalling mechanism in genetically engineered B cells that express either a single or a combination of IP3R subtypes, and show that Ca2+-signalling patterns depend on the IP3R subtypes, which differ significantly in their response to agonists, i.e. IP3, Ca2+ and ATP. IP3R-2 is the most sensitive to IP3 and is required for the long lasting, regular Ca2+ oscillations that occur upon activation of B-cell receptors. IP3R-1 is highly sensitive to ATP and mediates less regular Ca2+ oscillations. IP3R-3 is the least sensitive to IP3 and Ca2+, and tends to generate monophasic Ca2+ transients. Furthermore, we show for the first time functional interactions between coexpressed subtypes. Our results demonstrate that differential expression of IP3R subtypes helps to encode IP3-mediated Ca2+ signalling.  (+info)

The SH2 domain-containing inositol 5'-phosphatase (SHIP) recruits the p85 subunit of phosphoinositide 3-kinase during FcgammaRIIb1-mediated inhibition of B cell receptor signaling. (6/2715)

Coligation of FcgammaRIIb1 with the B cell receptor (BCR) or FcepsilonRI on mast cells inhibits B cell or mast cell activation. Activity of the inositol phosphatase SHIP is required for this negative signal. In vitro, SHIP catalyzes the conversion of the phosphoinositide 3-kinase (PI3K) product phosphatidylinositol 3,4, 5-trisphosphate (PIP3) into phosphatidylinositol 3,4-bisphosphate. Recent data demonstrate that coligation of FcgammaRIIb1 with BCR inhibits PIP3-dependent Btk (Bruton's tyrosine kinase) activation and the Btk-dependent generation of inositol trisphosphate that regulates sustained calcium influx. In this study, we provide evidence that coligation of FcgammaRIIb1 with BCR induces binding of PI3K to SHIP. This interaction is mediated by the binding of the SH2 domains of the p85 subunit of PI3K to a tyrosine-based motif in the C-terminal region of SHIP. Furthermore, the generation of phosphatidylinositol 3,4-bisphosphate was only partially reduced during coligation of BCR with FcgammaRIIb1 despite a drastic reduction in PIP3. In contrast to the complete inhibition of Tec kinase-dependent calcium signaling, activation of the serine/threonine kinase Akt was partially preserved during BCR and FcgammaRIIb1 coligation. The association of PI3K with SHIP may serve to activate PI3K and to regulate downstream events such as B cell activation-induced apoptosis.  (+info)

Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors. (7/2715)

We previously found that the adapter protein Gab1 (110 kD) is tyrosine-phosphorylated and forms a complex with SHP-2 and PI-3 kinase upon stimulation through either the interleukin-3 receptor (IL-3R) or gp130, the common receptor subunit of IL-6-family cytokines. In this report, we identified another adapter molecule (100 kD) interacting with SHP-2 and PI-3 kinase in response to various stimuli. The molecule displays striking homology to Gab1 at the amino acid level; thus, we named it Gab2. It contains a PH domain, proline-rich sequences, and tyrosine residues that bind to SH2 domains when they are phosphorylated. Gab1 is phosphorylated on tyrosine upon stimulation through the thrombopoietin receptor (TPOR), stem cell factor receptor (SCFR), and T-cell and B-cell antigen receptors (TCR and BCR, respectively), in addition to IL-3R and gp130. Tyrosine phosphorylation of Gab2 was induced by stimulation through gp130, IL-2R, IL-3R, TPOR, SCFR, and TCR. Gab1 and Gab2 were shown to be substrates for SHP-2 in vitro. Overexpression of Gab2 enhanced the gp130 or Src-related kinases-mediated ERK2 activation as that of Gab1 did. These data indicate that Gab-family molecules act as adapters for transmitting various signals.  (+info)

Involvement of wiskott-aldrich syndrome protein in B-cell cytoplasmic tyrosine kinase pathway. (8/2715)

Bruton's tyrosine kinase (Btk) has been shown to play a role in normal B-lymphocyte development. Defective expression of Btk leads to human and murine immunodeficiencies. However, the exact role of Btk in the cytoplasmic signal transduction in B cells is still unclear. This study represents a search for the substrate for Btk in vivo. We identified one of the major phosphoproteins associated with Btk in the preB cell line NALM6 as the Wiskott-Aldrich syndrome protein (WASP), the gene product responsible for Wiskott-Aldrich syndrome, which is another hereditary immunodeficiency with distinct abnormalities in hematopoietic cells. We demonstrated that WASP was transiently tyrosine-phosphorylated after B-cell antigen receptor cross-linking on B cells, suggesting that WASP is located downstream of cytoplasmic tyrosine kinases. An in vivo reconstitution system demonstrated that WASP is physically associated with Btk and can serve as the substrate for Btk. A protein binding assay suggested that the tyrosine-phosphorylation of WASP alters the association between WASP and a cellular protein. Furthermore, identification of the phosphorylation site of WASP in reconstituted cells allowed us to evaluate the catalytic specificity of Btk, the exact nature of which is still unknown.  (+info)

Defects in the gene encoding Brutons tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. Recent studies have shown that Btk is tyrosine phosphorylated and activated upon B cell antigen receptor (BCR) stimulation. To elucidate the functions of this kinase, we examined BCR signaling of DT40 B cells deficient in Btk. Tyrosine phosphorylation of phospholipase C (PLC)-gamma 2 upon receptor stimulation was significantly reduced in the mutant cells, leading to the loss of both BCR-coupled phosphatidylinositol hydrolysis and calcium mobilization. Pleckstrin homology and Src-homology 2 domains of Btk were required for PLC-gamma 2 activation. Since Syk is also required for the BCR-induced PLC-gamma 2 activation, our findings indicate that PLC-gamma 2 activation is regulated by Btk and Syk through their concerted actions. ...
Autophagy is a major pathway for degradation of cytoplasmic components, and is induced by some apoptotic stimuli mostly in cancer cells under the condition in which apoptosis is blocked. Ligation of the B cell antigen receptor (BCR) induces apoptosis and plays a crucial role in self-tolerance. However, whether BCR ligation induces autophagy is not clear. Here, we demonstrate that autophagosomes are extensively formed in normal mouse B cells as well as the WEHI-231 B cell line upon induction of BCR ligation-induced apoptosis regardless of whether apoptosis is blocked by overexpression of Bcl-2. In contrast, autophagosomes were not formed during apoptosis of spleen B cells cultured with medium alone or in BCR-ligated BAL17 cells which do not undergo apoptosis. Moreover, autophagy is not induced when apoptotic BCR signaling is abrogated by CD40 signaling. These results indicate that autophagy is induced specifically by apoptotic BCR signaling even in unmanipulated normal B cells.
Clone REA1168 regognizes the cytoplamic domain of CD79a, which is also known as MB-1 and Igα. Along with CD79b (Igβ), CD79a is associated with surface Ig (sIg) to form the B cell antigen receptor complex. CD79a is a 47 kDa glycoprotein and comprises a single extracellular immunoglobulin domain, a transmembrane domain, and a signaling intracellular domain with immunoreceptor tyrosine-based activation motif (ITAM). CD79a/CD79b heterodimer facilitates differentiation of pre-B cells from pro-B cells, surface expression of sIg, signal transduction following antigen recognition, and enodocytosis of recognised antigens. Surface expression of CD79a dimishes in plasma cells, where it is mainly found as an intracellular molecule. CD79 is considered a B cell-specific marker and is often used to identify the B cell lineage of acute lymphoblastic leukemia. Recent reports however suggest expression of CD79a in T cell acute lymphoblastic leukemia. Individuals lacking CD79a have low/absent circulating pre-B cells and
Background Immature B lymphocytes and certain B cell lymphomas undergo apoptotic cell death following activation of the B cell antigen receptor (BCR) signal transduction pathway. for the three C-terminal tyrosines was expressed in a murine B cell Rabbit Polyclonal to FER (phospho-Tyr402) lymphoma cell line, BCL1.3B3 to interfere with regular Syk regulation as a way to examine the Syk activation part of BCR signaling. Intro of the kinase-inactive mutant resulted in the constitutive activation from the endogenous wildtype Syk enzyme in the lack of receptor engagement through a dominant-positive impact. Under these circumstances, Syk kinase activation happened in the lack of phosphorylation on Syk tyrosine residues. Although Syk is apparently necessary for BCR-induced apoptosis in a number of systems, no upsurge in spontaneous cell loss of life was seen in these cells. Remarkably, even though the endogenous Syk kinase was energetic enzymatically, no improvement in the phosphorylation of ...
Despite very similar gene expression profiles, the clinical course of B-cell chronic lymphocytic leukemia (B-CLL) is heterogeneous. Immunoglobulin VH (IgVH) mutational status and expression of B-cell receptor (BCR) signaling mediators have been associated with disease progression. However, the consequences of BCR engagement on cell survival and evolution of the disease remain unclear. We show here that B-CLL cell survival is dependent on the threshold of BCR stimulation induced by immobilized antibody, in contrast to soluble anti-mu F(ab)2 antibody, which leads to apoptosis. Measurement of metabolic activity and apoptotic response discriminated two subgroups. Nonresponders showed low metabolic activity and unmodified apoptotic response upon BCR stimulation. In contrast, responders exhibited increased metabolic activity and inhibition of spontaneous apoptosis. This survival advantage was associated to a BCR-dependent activation profile leading to induction of cyclin D2/cyclin-dependent kinase 4
Ligation of membrane immunoglobulin M (mIgM) induces cell cycle arrest and apoptosis in the WEHI 231 B-lymphoma cell collection. show that resistance to apoptosis can arise as a result of mutations affecting discrete stages of the mIgM signalling pathway. The mutant lines reported here show defects that have not yet been recognized in previous studies and are likely to be useful tools in dissecting the signalling of cell death in W lymphocytes. Introduction Signals SKF 89976A HCl generated through membrane immunoglobulin on the surface of W lymphocytes can lead either to B-cell activation and proliferation or, alternatively, to programmed cell death or apoptosis, the greatest fate of the W cell depending on factors such as its developmental stage.1 Cross-linking of membrane immunoglobulin M (mIgM) generates a cascade of intracellular signals; in the beginning, quick tyrosine phosphorylation of non-receptor tyrosine kinases including SKF 89976A HCl syk, btk and users of the src-family, lyn, fyn, ...
Bolger-Munro, M., Choi, K., Cheung, F., Liu, Y. T., Dang-Lawson, M., Deretic, N., … Gold, M. R. (2021). The Wdr1-LIMK-Cofilin axis controls B cell antigen receptor-induced actin remodeling and signaling at the immune synapse. Frontiers in Cell and Developmental Biology. https://doi.org/10.3389/fcell.2021.649433 ...
Stimulation of immune cell receptors, such as the B cell receptor (BCR), can lead to multiple distinct cellular responses, making these cells excellent models for studying signal plasticity. Singh et al. found that inhibition of either release of calcium from the endoplasmic reticulum (with TMB-8) or uptake of calcium from the extracellular medium (with EGTA, a calcium chelator) produced a global dampening of BCR-dependent phosphorylation, including phosphorylation events that occurred within the first minute of BCR activation. Indeed, one of the events that was inhibited was the phosphorylation of Lyn, a Src family tyrosine kinase, which is believed to be the first enzyme activated in response to BCR ligand binding. This was surprising because calcium signals are downstream events; thus, this result suggested that calcium can feed back on the early signaling events. Formation of reactive oxygen species (ROS) in response to BCR activation occurred within seconds and was inhibited by ...
CD79b molecule, immunoglobulin-associated beta, also known as CD79B (Cluster of Differentiation 79B), is a human gene. It is associated with agammaglobulinemia-6. The B lymphocyte antigen receptor is a multimeric complex that includes the antigen-specific component, surface immunoglobulin (Ig). Surface Ig non-covalently associates with two other proteins, Ig-alpha and Ig-beta, which are necessary for expression and function of the B-cell antigen receptor. This gene encodes the Ig-beta protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described. Cluster of differentiation GRCh38: Ensembl release 89: ENSG00000007312 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000040592 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Entrez Gene: CD79B CD79b molecule, immunoglobulin-associated beta. Reth M (1992). Antigen receptors on B lymphocytes. Annu. Rev. Immunol. 10: 97-121. ...
These collective observations support a model in which a CD22, EndoU, and c-Myc expression axis controls B cell fate after BCR ligation in B6 mice. EndoU levels remain low in WT[B6] B cells, allowing robust c-Myc expression and cell cycle progression after BCR engagement. In contrast, chronically high EndoU expression by CD22−/−[B6] B cells prevents c-Myc up-regulation after BCR ligation, resulting in AICD. EndoU was a major regulator of AICD in CD22−/−[B6] and IgTgsHEL mice, although additional unknown mechanisms undoubtedly also contribute to this complex regulatory process.. EndoU overexpression in vivo also occurred in response to BCR signals generated in IgTgsHEL mice, where B cells displayed a CD5highHSAhighIgMlow phenotype and failed to up-regulate c-Myc expression as was observed in CD22−/−[B6] mice. Genetic deletion of EndoU normalized this B cell phenotype in a substantial number of IgTgsHEL mice, which correlated with robust anti-HEL auto-Ab responses at an early age in ...
The quantity and quality of signals from the B cell antigen receptor (BCR) drives the positive and negative selection of B lymphocytes and establishes the balance of tolerance and immunity. Experiments using immunoglobulin transgenic mice and mutations in key BCR signalling components have given insight into how the antigen receptor is tuned and how thresholds for qualitatively different outcomes are established and maintained. This research also describes how genetic variants can shift the balance between autoimmunity and tolerance.
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The B lymphocyte antigen receptor is a multimeric complex that includes the antigen-specific component, surface immunoglobulin (Ig). Surface Ig non-covalently associates with two other proteins, Ig-alpha and Ig-beta, which are necessary for expression and function of the B-cell antigen receptor. This gene encodes the Ig-alpha protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008 ...
In this study, it was shown that IL-4-mediated signals were strikingly but transiently inhibited by TCR engagement of naive T cells. This inhibition involved triggering of both the PKC-MAPK and calcineurin pathways. It has recently been reported by Ivashkiv and colleagues that the IL-2 signal was inhibited by TCR engagement in preactivated T cells and the inhibition was mediated by the PKC-MAPK pathway (35). We have also checked the IL-4 signal in activated cells and observed results quite similar to those described above for naive T cells (data not shown). In addition, we found that the IL-2 signal was also inhibited by TCR engagement in naive T cells. McMahon and colleagues have shown that sustained activation of the Raf-MEK-ERK pathway elicited cytokine unresponsiveness in T cells (46). These results are consistent in indicating that MAPK plays an important role in the cross-talk between TCR and cytokine signals. Our data further show that although MAPK activation is necessary, it is not ...
V region of the variable domain of immunoglobulin heavy chains that participates in the antigen recognition (PubMed:24600447). Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic
V region of the variable domain of immunoglobulin heavy chains that participates in the antigen recognition. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, ...
Measuring signaling kinetics allowed identification of two different ways the strength of BCR signaling is regulated in primary B cells. BCR-mediated signaling might be amplified by activating a greater number of the existing signaling molecules without changing activation and deactivation kinetics (i.e., more phosphorylated Syk per cell at a critical time). Alternatively, BCR signaling output might be altered by extending the time over which a given number of molecules in each cell were active, either by achieving maximal signaling more quickly or by extending the time at which maximum signaling is sustained. Our results show that B cells with an IgG BCR maintain ERK1/2 signaling over a significantly greater time than B cells with an IgM BCR (Fig. 2⇑). In contrast, our results in IgM isotype B cells show that PTPs were activated to remove phosphorylation of Syk and ERK1/2 within 4-8 min following BCR engagement (Figs. 2⇑ and 4⇑).. This contrast between weaker, transient signaling kinetics ...
Antigen receptor stimulation of mature alpha beta T lymphocytes can lead either to proliferation or death. Programmed cell death, termed apoptosis, leads to the clonal deletion of both thymocytes and mature T cells that establishes tolerance. How a mature T cell selects between proliferation and dea …
B cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor (BCR) is an integral membrane protein complex that is composed of two immunoglobulin (Ig) heavy chains, two Ig light chains and two heterodimers of Ig-alpha and Ig-beta. After BCR ligation by antigen, three main protein tyrosine kinases (PTKs) -the SRC-family kinase LYN, SYK and the TEC-family kinase BTK- are activated. Phosphatidylinositol 3-kinase (PI3K) and phospholipase C-gamma 2 (PLC-gamma 2) are important downstream effectors of BCR signalling. This signalling ultimately results in the expression of immediate early genes that further activate the expression of other genes involved in B cell proliferation, differentiation and Ig production as well as other processes ...
B cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor (BCR) is an integral membrane protein complex that is composed of two immunoglobulin (Ig) heavy chains, two Ig light chains and two heterodimers of Ig-alpha and Ig-beta. After BCR ligation by antigen, three main protein tyrosine kinases (PTKs) -the SRC-family kinase LYN, SYK and the TEC-family kinase BTK- are activated. Phosphatidylinositol 3-kinase (PI3K) and phospholipase C-gamma 2 (PLC-gamma 2) are important downstream effectors of BCR signalling. This signalling ultimately results in the expression of immediate early genes that further activate the expression of other genes involved in B cell proliferation, differentiation and Ig production as well as other processes ...
The advent of new live cell imaging techniques has provided both the temporal and spatial resolution over the time and length scales that are critical to decipher the earliest events in B cell activation. Although our understanding of these events is still incomplete, recent results from high resolution live cell imaging studies are providing the first glimpse into the process by which B cell signaling is initiated (9, 10, 38). Here we investigated the effect of colligating the FcγRIIB to the BCR through ICs on these early events, by imaging both the BCR and FcγRIIB during the first stages of B cell encounter of ICs incorporated into a planar lipid bilayer to mimic an APC surface. We conclude that the FcγRIIB blocks the earliest events in BCR activation including the formation of signaling active, immobile BCR oligomers and the transition of the cytoplasmic domains from a closed to a signaling active open conformation. The FcγRIIB accomplished this as it stably associated with raft ...
The CD79a molecule (MB-1, Igα) is part of the MB-1/B29 (CD79a/CD79b) disulfide-linked heterodimer which is non-covalently associated with membrane immunoglobulins (Igs) to build the B Cell antigen Receptor (BCR) complex.
We previously reported that B-cell receptor (BCR) signaling promoted a concomitant decrease of CXCR4 and CD62L membrane expression only in progressive cases of chronic lymphocytic leukemia (CLL). Recently, Quiroga and colleagues raised some challenging issues and pointed out discrepancies between the two reports.. In their letter, Quiroga and colleagues questioned our BCR stimulation protocol. Several studies, including ours, reported that soluble anti-immunoglobulin M (IgM) resulted in apoptosis, whereas immobilized anti-IgM or F(ab)2 fragment both sustained cell survival (1-3). Hence, the increased cell survival following soluble F(ab)2 exposure observed by Quiroga and colleagues is rather surprising.. We showed that downregulation of CXCR4 was associated with a reduced migration toward CXCL12. Our results are in agreement with numerous reports in various cell types including CLL cells (4). Quiroga and colleagues reported a similar CXCR4 decrease but associated to an unexplained increased ...
Figure 1. BCR development. The progenitor cell undergoes recombination of V, D, and J segments in the germline, which generates two identical heavy chains. Recombination of V and J segments generates two identical light chains. Random nucleotide additions or deletions at the junctions of the V, D, and J segments provide additional diversity. Furthermore, B cells activated by immune responses undergo somatic hypermutation (SHM), in which additional point mutations are introduced.. Understanding the profiles of BCRs, (i.e., sequencing the full-length CDR3 regions to determine the diversity of receptors and the clonotypes, defined by expression of specific H, K, and L gene segments) can not only aid in gaining insights into the adaptive immune response in healthy individuals, but also in those with a wide range of conditions, including infectious diseases, allergies, autoimmune disorders, cancers, and aging (Yaari & Kleinstein, 2015). Accurate determination of the clonotypes and isotypes expressed ...
Figure 1. BCR development. The progenitor cell undergoes recombination of V, D, and J segments in the germline, which generates two identical heavy chains. Recombination of V and J segments generates two identical light chains. Random nucleotide additions or deletions at the junctions of the V, D, and J segments provide additional diversity. Furthermore, B cells activated by immune responses undergo somatic hypermutation (SHM), in which additional point mutations are introduced.. Understanding the profiles of BCRs, (i.e., sequencing the full-length CDR3 regions to determine the diversity of receptors and the clonotypes, defined by expression of specific H, K, and L gene segments) can not only aid in gaining insights into the adaptive immune response in healthy individuals, but also in those with a wide range of conditions, including infectious diseases, allergies, autoimmune disorders, cancers, and aging (Yaari & Kleinstein, 2015). Accurate determination of the clonotypes and isotypes expressed ...
THE IgM B-CELL RECEPTOR a a THE IgM B-CELL RECEPTOR antigen binding mIg molecule H L V b a Ig-a/Ig-b heterodimer Signal transduction Lyn Kinases Syk Btk SHP-1 Phosphatases SLP-65/BLNK PLC HS1 Vav Adaptors + substrates
Chapter 6 Healthy humans have approximately 3x10 9 B-cells in the peripheral blood and this population encompasses the repertoire of distinct B-cells expressing different B- cell receptors (BCRs) necessary
We investigated the role of the T cell antigen receptor (TcR) in control of T cell migration in an in vitro system. We used T cells from transgenic mice bearing a TcR for the lysozyme peptide 48-62 bound to I-A(k) (3A9). T cells from the 3A9 TcR transgenic mice crawled on purified intercellular adhesion molecule-1 substrates, but strikingly, stopped upon interaction with the physiological ligand, i.e., the mouse I-A(k) with covalently attached hen egg white lysozyme peptide residues 48-62 complex. TcR-triggered stopping was reversible by treatment with adhesion-strengthening phorbol esters. The microtubule organizing center of stopped cells was positioned adjacent to the site of stable cell anchorage. Direct conversion of lymphocyte function associated-1 to the high-affinity conformation with antibodies also stopped T cells in a similar manner to antigen. Thus, physiological TcR engagement triggers a stop signal through lymphocyte function associated-1. We propose that the stop signal is an early and
B cell Ag receptor (BCR) signaling changes dramatically during B cell development, resulting in activation in mature B cells and apoptosis, receptor editing, or anergy in immature B cells. BCR signaling in mature B cells was shown to be initiated by the translocation of the BCR into cholesterol- and sphingolipid-enriched membrane microdomains that include the Src family kinase Lyn and exclude the phosphatase CD45. Subsequently the BCR is rapidly internalized into the cell. Here we show that the BCR in the immature B cell line, WEHI-231, does not translocate into lipid rafts following cross-linking nor is the BCR rapidly internalized. The immature BCR initiates signaling from outside lipid rafts as evidenced by the immediate induction of an array of phosphoproteins and subsequent apoptosis. The failure of the BCR in immature B cells to enter lipid rafts may contribute to the dramatic difference in the outcome of signaling in mature and immature B cells.
B-cell receptor (BCR) signaling pathways and interactions with the tumor microenvironment account for mantle cell lymphoma (MCL) cells survival in lymphoid organs. In several MCL cases, the WNT/β-catenin canonical pathway is activated and β-catenin accumulates into the nucleus. As both BCR and β-catenin are important mediators of cell survival and interaction with the microenvironment, we investigated the crosstalk between BCR and WNT/β-catenin signaling and analyzed their impact on cellular homeostasis as well as their targeting by specific inhibitors. β-catenin was detected in all leukemic MCL samples and its level of expression rapidly increased upon BCR stimulation. This stabilization was hampered by the BCR-pathway inhibitor Ibrutinib, supporting β-catenin as an effector of the BCR signaling. In parallel, MCL cells as compared with normal B cells expressed elevated levels of WNT16, a NF-κB target gene. Its expression increased further upon BCR stimulation to participate to the stabilization
TY - JOUR. T1 - The relationship between surface immunoglobulin isotype and immune function of murine b lymphocytes. T2 - II. Surface immunoglobulin isotopes on unprimed b cells in the spleen*. AU - Zan Bar, I.. AU - Vitetta, E. S.. AU - Strober, S.. N1 - Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 1977/5/1. Y1 - 1977/5/1. N2 - We investigated the ability of IgM-, IgD-, and IgG-bearing cells from the spleens of unprimed (BALB/c × C57BL/Ka)F1 mice to restore the adoptive primary anti-BSA and anti-DNP antibody responses. Purified populations of isotype-specific cells were prepared by immunofluorescent staining and sorting on the fluorescence activated cell sorter. Bright or dull cells were transferred to irradiated syngeneic recipients which were challenged with DNPoBSA in complete Freunds adjuvant. Unfractionated spleen cells as well as IgM- and IgDbearing cells restored the adoptive primary IgM and IgG antibody response. IgG-bearing cells restored a vigorous adoptive ...
Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Also required for BCR surface expression and for efficient differentiation of pro- and pre-B-cells. Stimulates SYK autophosphorylation and activation. Binds to BLNK, bringing BLNK into proximity with SYK and allowing SYK to phosphorylate BLNK. Also interacts with and increases activity of some Src-family tyrosine kinases. Represses BCR signaling during development of immature B-cells.
Intercellular adhesion molecule (ICAM) 1/CD54 plays an important role in T cell dependent B cell activation and for function of B lymphocytes as antigen-presenting cells. ICAM-1 expression is upregulated as a consequence of B lymphocyte antigen receptor (BCR) signaling, thereby serving to render antigen-stimulated B cells more receptive to T cell-mediated costimulatory signals. We have investigated BCR-induced expression of the Icam-1 gene in primary B cells and B cell lines and have found it to be dependent on BCR-induced expression of the transcription factor EGR1. Icam-1 transcription, induced by BCR cross-linking or bypassing the BCR with phorbol ester, is absent in a B cell line in which the EGR1-encoding gene (egr-1) is methylated and not expressed. A potential EGR1-binding site was located at -701 bp upstream of the murine Icam-1 gene transcription start site and shown by electrophoretic mobility shift assay to bind to murine EGR1. Mutation of this site in the context of 1.1 kb of the ...
Hepatitis C virus (HCV) causes B-cell lymphoproliferative disorders (LPDs) expressing stereotyped B-cell receptors (BCRs) endowed with rheumatoid factor (RF) activity and putatively recognizing the HCV E2 protein. To further untangle the shaping and function of these BCRs, we analyzed immunoglobulin gene rearrangements of monoclonal B cells from 13 patients with HCV-associated LPDs and correlated their features with the clinical outcomes of antiviral therapy. While only two patients shared a stereotyped heavy-chain complementarity determining region 3 (CDR3) sequence, two kappa chain CDR3 stereotyped sequences accounted for 77% of BCRs. Light chains were enriched in sequences homologous to anti-HCV E2 antibodies compared with heavy chains (7/13 vs. 0/13; p = 0.005). Anti-HCV E2 homology was uniquely associated (7/7 vs. 0/6; p = 0.0006) with a stereotyped CDR3 sequence encoded by IGKV3-20/3D-20 gene(s) accounting for 54% of BCRs. An IGKV3-15/IGKJ1-encoded stereotyped sequence homologous to WA RF
T-cell antigen receptor-induced signaling requires both ZAP-70 and Lck protein-tyrosine kinases. One essential function of Lck in this process is to phosphorylate ZAP-70 and up-regulate its catalytic activity. We have previously shown that after T-cell antigen receptor stimulation, Lck binds to ZAP-70 via its Src homology 2 (SH2) domain (LckSH2) and, more recently, that Tyr319 of ZAP-70 is phosphorylated in vivo and plays a positive regulatory role. Here, we investigated the possibility that Tyr319 mediates the SH2-dependent interaction between Lck and ZAP-70. We show that a phosphopeptide encompassing the motif harboring Tyr319, YSDP, interacted with LckSH2, although with a lower affinity compared with a phosphopeptide containing the optimal binding motif, YEEI. Moreover, mutation of Tyr319 to phenylalanine prevented the interaction of ZAP-70 with LckSH2. Based on these results, a gain-of-function mutant of ZAP-70 was generated by changing the sequence Y319SDP into Y319EEI. As a result of its increased
Clone REA499 recognizes the human and mouse CD27 antigen, a single-pass type I membrane protein, also known as tumor necrosis factor receptor superfamily member 7 (TNFRSF7). CD27 is a member of the nerve growth factor receptor family and is exclusively expressed on cells of the lymphoid lineage, mostly in an activation-specific manner, and all enhance T cell receptor (TCR)-induced T cell expansion. CD27 and its ligand, CD70, have been defined at the protein, cDNA, and genomic level in both human and mouse. It is found on natural killer (NK), T, and B cell populations. In human and mice, the majority of CD4+ and CD8+ naive peripheral T cells express CD27 and expression is up-regulated upon TCR stimulation. Loss of CD27 expression is irreversible and seems to represent terminal effector T cell differentiation. In humans, naive B cells lack CD27 but antigen receptor stimulation induces expression. CD27+ B cells display all the functional and phenotypic characteristics of memory cells. Additional
TY - JOUR. T1 - Effects of IL-4 and Fcγ receptor II engagement on Egr-1 expression during stimulation of B lymphocytes by membrane immunoglobulin crosslinking. AU - Klaus, Stephen J.. AU - Phillips, Nancy E.. AU - Parker, David C.. PY - 1993/11. Y1 - 1993/11. N2 - Egr-1 is an immediate early gene that is rapidly upregulated in response to mitogenic signals induced by antigen receptor crosslinking on murine B lymphocytes. It has been shown that levels of Egr-1 expression are closely correlated with B cell proliferation in several models of B cell activation and tolerance. We compared the expression of Egr-1 during B cell stimulation with Fab′2 and IgG anti-immunoglobulin (anti-IG), since it is known that Fab′2 anti-Ig is mitogenic while IgG anti-Ig is not, owing to a dominant inhibitory effect of crosslinking the B cell Fcγ RII to membrane Ig. While mitogenic doses of Fab′2 anti-Ig induce large and rapid increases in Egr-1 expression, IgG anti-Ig results in smaller increases in Egr-1 ...
We show here that approximately 25% of the mature peripheral B cells can survive in the mouse for at least 2 months without Syk, in a manner that requires BAFF‐R and CD19 signaling. In contrast, deletion of the Syk gene in early B cells results in the appearance of a small number of immature IgM+ B cells, which, however, fail to give rise to any mature B cells in the periphery (Cheng et al, 1995). Thus, pre‐B and mature B cells have different requirements for Syk. Indeed, the pre‐BCR is an autonomously signaling receptor that continuously engages Syk, whereas the BCR forms an autoinhibited oligomer on mature B cells that is not in contact with Syk. This notion is supported by a proximity ligation analysis showing that Syk is localized near the BCR only after BCR activation (Infantino et al, 2010; Klasener et al, 2014).. The presence of large amounts of Syk‐negative mature B cells in the induced mb1‐CreERT2;Sykfl/fl mice allowed us to analyze the in vivo role of this kinase in the ...
We show here that approximately 25% of the mature peripheral B cells can survive in the mouse for at least 2 months without Syk, in a manner that requires BAFF‐R and CD19 signaling. In contrast, deletion of the Syk gene in early B cells results in the appearance of a small number of immature IgM+ B cells, which, however, fail to give rise to any mature B cells in the periphery (Cheng et al, 1995). Thus, pre‐B and mature B cells have different requirements for Syk. Indeed, the pre‐BCR is an autonomously signaling receptor that continuously engages Syk, whereas the BCR forms an autoinhibited oligomer on mature B cells that is not in contact with Syk. This notion is supported by a proximity ligation analysis showing that Syk is localized near the BCR only after BCR activation (Infantino et al, 2010; Klasener et al, 2014).. The presence of large amounts of Syk‐negative mature B cells in the induced mb1‐CreERT2;Sykfl/fl mice allowed us to analyze the in vivo role of this kinase in the ...
Primary immunodeficiency diseases are inherited disorders that affect human adaptive and innate immunity. In most cases, affected individuals experience recurrent infections, but they may also suffer from autoimmune diseases and malignancies. This chapter focuses on Signal Transduction by T and B Lymphocyte Antigen Receptors, including the historic and scientific background, clinical presentations, immunologic characteristics, and the molecular/genetic underpinnings. Where appropriate, diagnostic tools and therapeutic options are outlined -- from prophylactic anti-infective measures to hematopoietic stem cell transplantation and gene therapy.
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Purpose: B-cell receptor signaling plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). However, blocking B-cell receptor signaling with dasatinib, an inhibitor of SRC kinase, produced variable results in preclinical and clinical studies. We aim to define the molecular mechanisms underlying the differential dasatinib sensitivity and to uncover more effective therapeutic targets in CLL.. Experimental Design: Fresh CLL B cells were treated with dasatinib, and cell viability was followed. The CLL cases were then divided into good and poor responders. The cellular response was correlated with the activities of B-cell receptor signaling molecules, as well as with molecular and cytogenetic prognostic factors.. Results: Among 50 CLL cases, dasatinib treatment reduced cell viability by 2% to 90%, with an average reduction of 47% on day 4 of culture. The drug induced CLL cell death through the intrinsic apoptotic pathway mediated by reactive oxygen species. Unexpectedly, ...
Fingerprint Dive into the research topics of Cell surface immunoglobulin. XI. The appearance of an IgD like molecule on murine lymphoid cells during ontogeny. Together they form a unique fingerprint. ...
The immune system plays a powerful and central role in human health. The adaptive arm of the immune system consists of B and T cells that recognize antigen using lymphocyte antigen receptors, whose functionality and specificity is derived from gene rearrangements that form the T cell receptor (TCR) and B cell receptor (BCR). Methods to profile the phenotype and repertoire of immune cells typically rely on expensive single-cell sorting based approaches and are difficult to apply to low-input clinical samples, where antigen-specific cells are scarce. Towards this end, we have developed technologies that enable the profiling of single-cell transcriptomes with high resolution and scalability as well as the recovery and sequencing of lymphocyte antigen receptors. This allows us the ability to profile large numbers of cells recovered from clinical samples, to analyze the phenotypes of T and B cells in the context of their clonal lineages, and infer the epitope specificities of individual T and B ...
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The two major classes of antigen receptors on murine B lymphocytes, mIgM and mIgD, are both contained in a complex with two additional molecules, Ig-alpha and Ig-beta, which permit signal transduction. Accordingly, early biochemical events after antigen binding to either receptor are similar; biolog …
Cumulative evidence indicates that the CD19 coreceptor can induce positive signals that could enhance B cell responses. By regulating Src kinases and PI3K activity, it lowers the threshold of BcR-mediated signaling. Strikingly, study of CD19-/- mice revealed an apparent tight regulation of CD19 cell surface density during B cell development (Saito et al., 2002). In contrast to mice that overexpress CD19, CD19-/- mice have a markedly elevated BcR signaling threshold compared with wild-type mice. Reversibly, transgenic expression of low levels of human CD19 with normal levels of mouse CD19 resulted in hyperactive B cells and loss of tolerance to nuclear Ags (Sato etal., 2000). Since the product of PI3K, phosphatidyl inositol 3,4,5 trisphosphate, activates protein kinase B (PKB), which in turn promotes B cell survival, CD19 participates positively in B cell activation. Its positive effect on PI3K activity also may result in survival of immature B cells with low-affinity-binding BcRs, a potential ...
Phospholipase C (PLC) cleaves phosphatidylinositol 4,5-bisphosphate to form the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. Recently, PLC-L2, a PLC-like protein that lacks lipase activity, has been identified in skeletal muscle, as well as in B and T lymphocytes. Takenaka et al. generated PLC-2-deficient mice to investigate the possible role of PLC-2 signaling in B lymphocytes. PLC-L2-deficient mature B cells showed an enhanced proliferative response and increased expression of the activation marker CD69 after B cell receptor (BCR) stimulation in vitro, and mice displayed increased production of immunoglobulin M (IgM), IgG1, and IgG3 in response to antigen treatment in vivo. The authors used fura-2 imaging to show that Ca2+ influx after BCR stimulation was enhanced in PLC-2-deficient cells; moreover, translocation of nuclear factor of activated T cells (which is regulated by calcineurin, which is itself calcium-dependent) was enhanced. Finally, PLC-2-deficient cells showed ...
B-cell malignancies are heterogeneous diseases, and despite recent therapeutic advances, a high proportion of patients relapse or are refractory to treatment (1). Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and is characterized by the accumulation of clonal nonfunctional B lymphocytes in blood, bone marrow, lymph nodes, spleen, and liver (2). The clinical course of disease varies significantly; some patients have indolent disease and survive many years without therapy, whereas others experience rapidly fatal disease (3). The emergence of anti-CD20 antibody (rituximab)-based chemoimmunotherapy has led to significant progress in lymphoma and CLL therapy. However, because disease progression is inevitable, novel drugs are needed to improve long-term management (1, 4).. Agents targeting B-cell receptor (BCR) signaling through its downstream effectors phosphoinositide 3-kinase (PI3K) and Brutons tyrosine kinase (BTK) have emerged as promising treatment options ...
Anti-inflammatory cytokines are IL-4, IL-10, IL-11, IL-13, IL-16, transforming growth factor β, soluble TNF-receptor and soluble interleukin-1 receptor. » ... « The alveolar bone proper is 0.1 to 0.4 mm thick and is consisted of a Harversian system and lamellated and bundle bone. » ... « The immune response to infection is regulated by the balance between T helper (Th) 1 and Th2 cytokines. The differentiation of Th1 and Th2 T cell subsets is determined by a number of factors, including the antigen itself, antigen dose, route of administration, nature of the antigen-presenting cell and co-stimulatory molecules. » ... « Lymphocytes comprise 20-40% (1000 - 4000 cells/μl) of all leukocytes. » ... « Markers/Receptors on B cells are Surface Immunoglobulin (IgM and IgD), CD40, B7, ICAM-1, LFA-1, MHC II, CD32 (Ig Fc receptor), CD35 (Receptor for complement component). » ... « Genes for HLA are clustered in MHC located on Chromosome 6: 6p21. » ... « Most leukotoxin producing strains of A. ...
Anti-inflammatory cytokines are IL-4, IL-10, IL-11, IL-13, IL-16, transforming growth factor β, soluble TNF-receptor and soluble interleukin-1 receptor. » ... « The alveolar bone proper is 0.1 to 0.4 mm thick and is consisted of a Harversian system and lamellated and bundle bone. » ... « The immune response to infection is regulated by the balance between T helper (Th) 1 and Th2 cytokines. The differentiation of Th1 and Th2 T cell subsets is determined by a number of factors, including the antigen itself, antigen dose, route of administration, nature of the antigen-presenting cell and co-stimulatory molecules. » ... « Lymphocytes comprise 20-40% (1000 - 4000 cells/μl) of all leukocytes. » ... « Markers/Receptors on B cells are Surface Immunoglobulin (IgM and IgD), CD40, B7, ICAM-1, LFA-1, MHC II, CD32 (Ig Fc receptor), CD35 (Receptor for complement component). » ... « Genes for HLA are clustered in MHC located on Chromosome 6: 6p21. » ... « Most leukotoxin producing strains of A. ...
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Brown, L D.; Shen, F W.; Uhr, J W.; and Vitetta, E S., The expression of lyb-2.1 On murine b lymphocytes. Abstr. (1978). Subject Strain Bibliography 1978. 1222 ...
mouse Dbnl protein: a 55 kDa actin-binding cytoskeleton adapter protein that is coupled to signal transduction from lymphocyte antigen receptors; a substrate for Src & Syk kinases; isolated from mouse; RefSeq NM_013810
The B-cell Antigen receptor constitutes a disulphide linked heterodimer, consisting of CD79a (mb1) and CD79b / B29 polypeptides which are
Depletion of XIAP restores caspase-3 processing and activity. Cytosolic extracts of L1236 and KMH2 cells and of control B cell L1309 were prepared, and equal am
Comparison of TLR4 ligand-exposed or nonexposed B cells in the iLN by intravital TP-LSM. (A) Imaging. Labeled LPS-activated and control B cells were transferr
Complete information for BCAP31 gene (Protein Coding), B-Cell Receptor Associated Protein 31, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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Somatic assembly of T cell receptor and B cell receptor (BCR) genes produces a vast diversity of lymphocyte antigen recognition capacity. The advent of ...
The Enzyme Collection contains over 550 mAbs that recognize catalytic domains or associated regulatory subunits in enyme complexes
LYN-1604 is a potential ULK1 agonist with IC50 of 1.66 μM against MDA-MB-231 cells and it binds to wild-type ULK1 with a binding affinity in the nanom... Quality confirmed by NMR & HPLC. See customer reviews, validations & product citations.
Non-expression of Duffy antigen on red cells Miller, et al. 1976 P. vivax Non-expression of Duffy antigen on red cells Miller ... Gerbich antigen receptor negativity[edit]. Main article: Gerbich antigen system. The Gerbich antigen system is an integral ... Sickle-cell[edit]. Main article: Sickle-cell anemia. See also: Sickle-cell trait and Evolutionary_baggage § Sickle-Cell and ... Duffy antigen receptor negativity[edit]. Main article: Duffy antigen system. Plasmodium vivax has a wide distribution in ...
Weiss A, Littman DR (January 1994). "Signal transduction by lymphocyte antigen receptors". Cell. 76 (2): 263-74. doi:10.1016/ ... These immune cells include T cells, B cells, NK cells, dendritic cells, macrophages and mast cells. ITIMs have similar ... the activating NK cell receptor NKp44 contains an ITIM, but this seems to be non-functional. Some of the important receptors ... containing receptors, resulting in an innate inhibition mechanism within cells. ITIM bearing receptors have important role in ...
... a kind of Fc receptor called FcεRI) on the surface of other kinds of immune cells called mast cells and basophils, which are ... 1 - antigen. 2 - IgE antibody. 3 - FcεRI receptor. 4 - preformed mediators (histamine, proteases, chemokines, heparin). 5 - ... Cross-linking of the IgE and Fc receptors occurs when more than one IgE-receptor complex interacts with the same allergenic ... causes a response in a type of immune cell called a TH2 lymphocyte, which belongs to a subset of T cells that produce a ...
IgE can upregulate the expression of both types of Fcε receptors. FcεRI is expressed on mast cells, basophils, and the antigen- ... Receptors[edit]. IgE primes the IgE-mediated allergic response by binding to Fc receptors found on the surface of mast cells ... receptor FcεRII, or CD23.[23] CD23 may also allow facilitated antigen presentation, an IgE-dependent mechanism whereby B cells ... presenting dendritic cells in both mice and humans. Binding of antigens to IgE already bound by the FcεRI on mast cells causes ...
Kurosaki T (1999). "Genetic analysis of B cell antigen receptor signaling". Annu. Rev. Immunol. 17 (1): 555-92. doi:10.1146/ ... protein encoded by this gene functions as a docking protein acting downstream of Tec tyrosine kinase in B cell antigen receptor ... A mouse ortholog, stem cell adaptor protein 1, shares 83% identity with its human counterpart. STAP1 has been shown to interact ... the stem-cell-specific adaptor protein containing PH and SH2 domains". Biochem Biophys Res Commun. 268 (3): 697-703. doi: ...
A5 antigen (a developmentally-regulated cell surface protein; Xenopus nrp1; P28824); and receptor-like tyrosine protein ... It is an extracellular domain found in many receptors. A 170 amino acid domain, the so-called MAM (meprin, A-5 protein, and ... Takagi S, Hirata T, Agata K, Eguchi G, Fujisawa H, Mochii M (1991). "The A5 antigen, a candidate for the neuronal recognition ... These proteins have a modular, receptor-like architecture comprising a signal peptide, an N-terminal extracellular domain, a ...
2005). "Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells ... Tissue Antigens. 58 (4): 255-8. doi:10.1034/j.1399-0039.2001.580406.x. PMID 11782277. "Entrez Gene: NCR3 natural cytotoxicity ... 2003). "Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to ... 2005). "Evidence that the cellular ligand for the human NK cell activation receptor NKp30 is not a heparan sulfate ...
"Structural and functional characterization of a novel T cell receptor co-regulatory protein complex, CD97-CD55". The Journal of ... Eichler W, Hamann J, Aust G (Nov 1997). "Expression characteristics of the human CD97 antigen". Tissue Antigens. 50 (5): 429-38 ... CD97 is widely expressed on, among others, hematopoietic stem and progenitor cells, immune cells, epithelial cells, muscle ... Aust G, Wandel E, Boltze C, Sittig D, Schütz A, Horn LC, Wobus M (Apr 2006). "Diversity of CD97 in smooth muscle cells". Cell ...
Davis, Mark M.; Bjorkman, Pamela J. (1988). "T-cell antigen receptor genes and T-cell recognition". Nature. 334 (6181): 395-402 ... Davis is well known for identifying the first T-cell receptor genes, which are responsible for T lymphocytes ability to "see" ... "2021 Szent-Györgyi Prize Awarded to Pioneering Research Duo Who Have Paved the Path to Life-Saving T-Cell Receptor-Based Cancer ... the demonstration that T cells are able to detect and respond to even a single molecule of their ligand-fragments of antigens ...
CD44 antigen, the main cell surface receptor for HA. Hyaladherin "Link domain signature and profile". PROSITE. December 2004. ... which may be involved in cell-cell and cell-matrix interactions during inflammation and tumourigenesis; ... a hyaluronan-binding domain involved in extracellular matrix stability and cell migration". Cell. 86 (5): 767-75. doi:10.1016/ ... It is important in blood cell migration and apoptosis. The link domain is found in some extracellular proteins in vertebrates ...
Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors ... The process as a whole results in an effector cell, typically a T-cell, that can recognize a tumor cell antigen in a manner ... cytotoxic proteins and proliferation of T cells to kill CD19 B cells. Chimeric antigen receptors (CARs) have been developed as ... T cells purified from each person are modified by a virus that inserts genes that encode a chimaeric antigen receptor into ...
Patel, K.J.; Neuberger, M.S. (1993). "Antigen presentation by the B cell antigen receptor is driven by the αβ sheath and occurs ... Patel, Ketan Jayakrishna (1994). Antigen presentation by the B cell antigen receptor (PhD thesis). University of Cambridge. ... Such crosslinks are lethal to cells since they would prevent DNA from being copied (DNA replication) or for the genes it ... Patel's research is mainly concerned with how living cells repair DNA crosslinks. These lesions cause the two opposing strands ...
"The B-cell antigen receptor of the five immunoglobulin classes". Nature. 352 (6338): 777-81. Bibcode:1991Natur.352..777V. doi: ... Cell. 36 (3): 681-8. doi:10.1016/0092-8674(84)90348-9. PMID 6421489. S2CID 54312675. Ellison J, Hood L (Mar 1982). "Linkage and ... Cell. 29 (2): 691-9. doi:10.1016/0092-8674(82)90185-4. PMID 6288268. S2CID 54345379. Ellison J, Buxbaum J, Hood L (1983). " ... "Cloning and sequence determination of the gene for the human immunoglobulin epsilon chain expressed in a myeloma cell line". ...
... as effector cells for antibody-mediated killing via CD16 modified cells and as effector cells for chimeric antigen receptor ( ... NK-92 cells can be genetically engineered to recognize and kill human cancer cells. Chimeric Antigen Receptor (CAR) engineered ... NK-92 cells, like blood NK cells, can attack cancer cells if the tumor has not grown out of control. NK-92 cells were isolated ... Porter DL, Levine BL, Kalos M, Bagg A, June CH (August 2011). "Chimeric antigen receptor-modified T cells in chronic lymphoid ...
"Actin restricts FcɛRI diffusion and facilitates antigen-induced receptor immobilization". Nature Cell Biology. 10 (8): 955-963 ... Meanwhile, the formation of engaged receptor clusters might lead to de novo polymerization of actin filaments at the receptor ... Kusumi A, Sako Y (August 1996). "Cell surface organization by the membrane skeleton". Current Opinion in Cell Biology. 8 (4): ... Receptor monomers can hop across the inter-compartment boundaries quite readily, but when they form oligomers, their size ...
"Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia". New England Journal of Medicine. 365 (8): 725-733. ... American cell phone service provider Sprint Nextel reportedly pays $20 billion for rights to Apple's next mobile phone. October ... January 20 - In a landmark study that will ultimately see the cure for AIDS, a new technique renders T-Cells resistant to HIV. ... The United States Department of Justice files a lawsuit in an attempt to stop the $39 billion merger between cell phone giants ...
... and KIR2DL4 in antigen presenting cells, NK cells, and T cells". FASEB J. 19 (6): 662-4. doi:10.1096/fj.04-1617fje. PMID ... 2002). "Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4". Nat. Immunol. 3 ... "Isotypic variation of novel immunoglobulin-like transcript/killer cell inhibitory receptor loci in the leukocyte receptor ... The receptor can also function in antigen capture and presentation. It is thought to control inflammatory responses and ...
McGreal E, Miller J, Gordon S (2005). "Ligand recognition by antigen-presenting cell C-type lectin receptors". Curr Opin ... a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells". Cell. 100 (5): 587-97. doi:10.1016/ ... DC-SIGN is a C-type lectin receptor present on the surface of both macrophages and dendritic cells. DC-SIGN on macrophages ... Cambi A, Figdor CG (2004). "Dual function of C-type lectin-like receptors in the immune system". Curr. Opin. Cell Biol. 15 (5 ...
... that are rearranged during the development of the lymphocyte to provide that cell with a unique antigen receptor. The T cell ... B cell receptor T cell receptor Basel Institute for Immunology Charles M. Steinberg NKT cell Recombination-activating gene "The ... Most T-cell receptors are composed of a variable alpha chain and a beta chain. The T cell receptor genes are similar to ... V(D)J recombination allows for the generation of immunoglobulins and T cell receptors to antigens that neither the organism nor ...
... with Androgen receptor variant expression similar to that of AR-V7High VCaP cells. Notably, LN95 cells are significantly more ... LNCaP cells also express Prostate Specific Antigen (PSA). In vivo, Male mice develop tumors earlier and at a greater frequency ... LNCaP cells are a cell line of human cells commonly used in the field of oncology. LNCaP cells are androgen-sensitive human ... C4-2B cells produce and retain approximately 8x more mineralized calcium than parental LNCaP cells. C4-2B cells also express ...
2005). "Investigation of killer cell immunoglobulin-like receptor gene diversity V. KIR3DL2". Tissue Antigens. 64 (3): 226-34. ... Killer cell immunoglobulin-like receptor 3DL2 is a protein that in humans is encoded by the KIR3DL2 gene. Killer cell ... 2000). "Diversity of the p70 killer cell inhibitory receptor (KIR3DL) family members in a single individual". Mol. Cells. 10 (1 ... "The natural killer cell receptor specific for HLA-A allotypes: a novel member of the p58/p70 family of inhibitory receptors ...
Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen-presenting cells. Nature. 363(6425): pgs. 156-159 ... He and Emil R. Unanue were responsible for the discovery that antigen-presenting cells present antigens to bind to a special ... 1601-1608 Kersh EN, Shaw AS, Allen PM (1998). Fidelity of T cell activation through multistep T cell receptor ζ phosphorylation ... Separation of IL-4 production from Th cell proliferation by an altered T cell receptor ligand. Science. 252(5010): pgs. 1308- ...
"Association between killer-cell immunoglobulin-like receptor genotypes and leprosy in Brazil". Tissue Antigens. 72 (5): 478-82 ... Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets ... Killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 1 is a protein that in humans is encoded by the ... "Entrez Gene: Killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 1". Kimoto Y, Horiuchi T, Tsukamoto ...
Yang, Jianying; Reth, Michael (September 2010). "Oligomeric organization of the B-cell antigen receptor on resting cells". ... thus forming the B-cell antigen receptor (BCR). This occurs in a similar manner to the association of CD3 with the T-cell ... Engels N, Wollscheid B, Wienands J (Jul 2001). "Association of SLP-65/BLNK with the B cell antigen receptor through a non-ITAM ... Flaswinkel H, Reth M (1992). "Molecular cloning of the Ig-alpha subunit of the human B-cell antigen receptor complex". ...
2001). "Ch3 Antigen Recognition by B-Cell and T-cell Receptors". Immunobiology: The Immune System in Health and Disease (5th ed ... antigens can cause systemic anaphylaxis in mice through classic pathway by cross-linking IgE bound to the mast cell receptor Fc ... IgG antibodies can prevent IgE mediated anaphylaxis by intercepting a specific antigen before it binds to mast cell-associated ... IgG affinity to Fc receptors on phagocytic cells is specific to individual species from which the antibody comes as well as the ...
"Characterization of antigen receptor response elements within the interleukin-2 enhancer". Mol Cell Biol. 8 (4): 1715-24. doi: ...
This is analogous to the self signals provided by MHC class I molecules to NK cells via Ig-like or Ly49 receptors. NB. Protein ... 1997). "BIT, an immune antigen receptor-like molecule in the brain". FEBS Lett. 411 (2-3): 327-34. doi:10.1016/S0014-5793(97) ... 2001). "Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulator ... SIRPα recognizes CD47, an anti-phagocytic signal that distinguishes live cells from dying cells. CD47 has a single Ig-like ...
1996). "REceptors in proximal tubular epithelial cells for tubulointerstitial nephritis antigen". Kidney Int. 49 (1): 153-7. ... Tubulointerstitial nephritis antigen is a protein that in humans is encoded by the TINAG gene. TINAG is a basement membrane ... 1999). "Tubulointerstitial nephritis antigen (TIN-ag) is expressed in distinct segments of the developing human nephron". ... Kim SH, Kaminker P, Campisi J (1999). "TIN2, a new regulator of telomere length in human cells". Nat. Genet. 23 (4): 405-12. ...
"An unusual inhibitory receptor-the mast cell function-associated antigen (MAFA)". Molecular Immunology. 38 (16-18): 1307-1313. ... MAFA (Mast cell function-associated antigen) is a type II membranal glycoprotein, first identified on the surface of rat ... The inhibitory capacity of MAFA is best defined in mast cells, where MAFA keeps in check the antigen-induced (i.e. Fc epsilon ... More recently, human and mouse homologues of MAFA have been discovered yet also (or only) expressed by NK and T-cells. The ...
"Association of SWAP-70 with the B cell antigen receptor complex". Proc Natl Acad Sci U S A. 97 (5): 2180-4. doi:10.1073/pnas. ... 2004). "SWAP-70 identifies a transitional subset of actin filaments in motile cells". Mol. Biol. Cell. 14 (8): 3242-53. doi: ... Ihara S, Oka T, Fukui Y (2006). "Direct binding of SWAP-70 to non-muscle actin is required for membrane ruffling". J. Cell Sci ... Borggrefe T, Wabl M, Akhmedov AT, Jessberger R (1998). "A B-cell-specific DNA recombination complex". J. Biol. Chem. 273 (27): ...
These are made into synthetic receptors for T-Cells collected from the patient that are used to combat the disease. Competing ... Instead, one could cleave in a section between the bead and the antigen to elute. Since the pIII is intact it does not matter ... Then the expression of single chain Fv's (scFv), and single chain T cell receptors (scTCR) were expressed both with and without ... "CAR T Cells: Engineering Patients' Immune Cells to Treat Their Cancers". National Cancer Institute. 2013-12-06. Retrieved 9 ...
The ABH-antigen produced is thought to act as a receptor for human norovirus: A non-functional fucosyltransferase FUT2 provides ... Entry into the host cell is achieved by attachment to host receptors, which mediates endocytosis. Positive-stranded RNA virus ... which contains antigen-presenting sites and carbohydrate-receptor binding regions. Groups 1, 2, 3, and 4 last shared a common ... "The P Domain of Norovirus Capsid Protein Forms Dimer and Binds to Histo-Blood Group Antigen Receptors". J. Virol. 78 (12): 6233 ...
... and cell death. Daxx interacts with the TGF-β type II receptor by binding of C-terminal domain of the protein. When the cell is ... It interacts with a wide variety of proteins, such as apoptosis antigen Fas, centromere protein C, and transcription factor ... At the level of the cell, Daxx is found in the cytoplasm, interacting with Fas-receptor or other cytoplasmic molecules, as well ... Another important cell death-property of Daxx is the association with PML-NB. It was shown that Daxx associates with Pml only ...
Leukocyte immunoglobulin-like receptor subfamily A member 3 (LILR-A3) also known as CD85 antigen-like family member E (CD85e), ... an inhibitory receptor expressed on effector and memory CD8 T cells) with their HLA ligands, thus modulating immune reactions ... and dendritic cells involved in antigen processing". The Journal of Experimental Medicine. 185 (10): 1743-51. doi:10.1084/jem. ... "A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells ...
When a cytotoxic cell discovers any infected cell the content of the cytotoxic granules is released by receptor-mediated ... 15 kDa plays other roles in immunological processes, such as in antigen-presenting cell maturation and in immune cell migration ... Its expression is restricted to cytotoxic immune cells such as cytotoxic T cells, NK cells, NKT cells and γδ T cells. Orthologs ... such as NK cells, cytotoxic T cells, helper T cells, and in higher concentrations, immature dendritic cells. The 9 kDa form ...
Follicular DCs receptors CR1, CR2 and FcγRIIb trap antigen opsonized by complement or antibodies. These antigens are then taken ... Noncognate (not antigen specific) B cells play a significant role in the transport of antigens to FDCs. They capture immune ... Activated B-cells with low affinity to antigen captured on FDCs surface as well as autoreactive B-cells undergo apoptosis, ... TNF-a binds on the TNFRI receptor, while LT interacts with LTβ-receptor expressed on FDC precursors. In mice lacking B cells, ...
... or the part of an antigen to which B cell and T cell receptors recognize and bind. There is a large diversity of epitopes ... B and T cells are presented with self antigen after developing receptors while they are still in the primary lymphoid organs. ... This occurs after the functional B-cell receptor (BCR) is assembled. It is possible for B cells with high self affinity to go ... Clonal deletion is the removal through apoptosis of B cells and T cells that have expressed receptors for self before ...
Both rOmpA and rOmpB are members of a family of surface cell antigens (Sca) which are autotransporter proteins; they act as ... Then, the bacteria induce their internalization into host cells via a receptor-mediated invasion mechanism. Researchers believe ... Bacterial replication in host cells causes endothelial cell proliferation and inflammation, resulting in mononuclear cell ... This species of Rickettsia uses an abundant cell surface protein called OmpB to attach to a host cell membrane protein called ...
"Cell cycle regulated expression of nucleolar antigen P120 in normal and transformed human fibroblasts". J. Cell. Physiol. 154 ( ... Jallal B, Mossie K, Vasiloudis G, Knyazev P, Zachwieja J, Clairvoyant F, Schilling J, Ullrich A (1997). "The receptor-like ... The protein encoded by this gene is a nucleolar antigen expressed in proliferating cells. It is not detectable in non- ... Cell. 127 (3): 635-48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573. v t e. ...
A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells". Journal of ... "Peripheral blood-derived CD34+ progenitor cells: CXC chemokine receptor 4 and CC chemokine receptor 5 expression and infection ... as a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of ... Cells expressing CD34 (CD34+ cell) are normally found in the umbilical cord and bone marrow as haematopoietic cells, or in ...
It is important in maintaining basic cellular functions such as DNA replication, RNA transcription, cell division and cell ... Pra1 (pH regulated antigen 1) is a candida albicans protein that scavenges host zinc. Diagnosis is typically made based on ... These effects may be mediated by the defective functioning of estrogen via the estrogen receptor, which contains a zinc finger ... Wilson's disease, sickle cell disease, chronic kidney disease, chronic liver disease have all been associated with zinc ...
... lymphocyte function-associated antigen). It elicits shedding of CD23. It downregulates the B cell receptor. It induces ... cells in destroying these B cells. When an NK cell latched onto the cap, it had an 80% success rate at killing the cell. In ... The antibody binds to the cell surface protein CD20. CD20 is widely expressed on B cells, from early pre-B cells to later in ... as pathogenic B cells while sparing plasma cells and hematopoietic stem cells as they do not express the CD20 surface antigen. ...
... uteroglobin-like antigen (UGL), blastokinin, club-cell secretory protein (CCSP), Clara-cell 16 kD protein (17 in rat/mice), ... 2001). "A two-receptor pathway for catabolism of Clara cell secretory protein in the kidney". J. Biol. Chem. 276 (16): 13295- ... "Clara cell secretory protein deficiency alters clara cell secretory apparatus and the protein composition of airway lining ... 1994). "Clara cell 10 kDa protein mRNA in normal and atypical regions of human respiratory epithelium". Int. J. Cancer. 58 (5 ...
Finally, NADA can prevent the degranulation and release of TNF from RBL- 2H3 mast cells treated with an IgE-antigen complex. ... N-Arachidonoyl dopamine (NADA) is an endocannabinoid that acts as an agonist of the CB1 receptor and the transient receptor ... Additionally, NADA has been observed to suppress inflammatory activation of human Jurkat T cells and to inhibit the release of ... NADA was first described as a putative endocannabinoid (agonist for the CB1 receptor) in 2000 and was subsequently identified ...
... the PD-1 receptor on activated T-cells binds to ligands PD-L1 or PD-L2 on other cells, deactivating a potential T-cell-mediated ... tend to generate many mutated proteins that could serve as tumor antigens; pembrolizumab appears to facilitate clearance of any ... It targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes. It works by targeting the cellular pathway of ... This receptor is generally responsible for preventing the immune system from attacking the body's own tissues; it is a so- ...
Cell 36:879-888. Rao A, Faas S and H. Cantor. Analogues which compete for antigen binding to an arsonate-reactive T cell clone ... Engagement of the Type I interferon receptor on dendritic cells inhibits promotion of Th17 cells: central role of intracellular ... Glimcher L, Shen F-W, Cantor H. Identification of a cell-surface antigen selectively expressed on the natural killer cell. J. ... Glimcher L, Shen FW, Cantor H. Identification of a cell-surface antigen selectively expressed on the natural killer cell. J Exp ...
... is a receptor protein which is expressed on T cells and NK cells and shares sequence similarity with CD226 (also known as ... "Enhanced ADCC activity of affinity maturated and Fc-engineered mini-antibodies directed against the AML stem cell antigen CD96 ... promotes NK cell-target cell adhesion by interacting with the poliovirus receptor (CD155)". J. Immunol. 172 (7): 3994-8. doi: ... The protein may play a role in the adhesion of activated T and NK cells to their target cells during the late phase of the ...
... the mouse NK cell-associated antigen recognized by DX5 monoclonal antibody is CD49b (alpha 2 integrin, very late antigen-2)". ... Porter JC, Hogg N (1999). "Integrins take partners: cross-talk between integrins and other membrane receptors". Trends Cell ... They are found on a wide variety of cell types including T cells (the NKT cells), NK cells, fibroblasts and platelets. ... Integrins are involved in cell adhesion and also participate in cell-surface-mediated signalling. Expression of CD49b in ...
... including immunoglobulin-like killer cell receptors (KIR) that predominantly recognize antigens of class I human leukocyte ... KIR2DL3, Killer cell immunoglobulin-like receptor 2DL3 is a transmembrane glycoprotein expressed by the natural killer cells ... Have the ability to lyse target cells without prior sensitization antigen and regulate the immune responses by secreting ... "NK Cells Expressing the Inhibitory Killer Immunoglobulin-Like Receptors (iKIR) KIR2DL1, KIR2DL3 and KIR3DL1 Are Less Likely to ...
In Drosophila testicles, the Leukocyte-antigen-related (LAR) receptor tyrosine phosphatase targets selection and synapse ... cells continuously duplicate their genetic information without division into two cells. This creates very large cells, but ... These stem cells are important to the reproduction of Drosophila as they turn into sperm cells. ... the receptor expression is increased in the analysis of testicles containing higher numbers of early germ cells and cyst cells ...
Médicale Retinal gene therapy using lentiviral vectors Viral vector Lentiviral vector in gene therapy Chimeric antigen receptor ... "Novartis receives first ever FDA approval for a CAR-T cell therapy, Kymriah(TM) (CTL019), for children and young adults with B- ... This discovery enabled the development of lentiviral vectors that can infect non-dividing cells, contrary to other types of ... "Kite Pharma and bluebird bio Announce Strategic Collaboration to Advance Second Generation TCR Cell Therapy Products to Treat ...
For example, tuft cells that are in the urethra respond to bitter compounds, through activation of the taste receptor. This ... and as pulmonary brush cells in the respiratory tract, from nose to alveoli. A loss of tolerance to antigens that appear in the ... Play media Tuft cells are chemosensory cells in the epithelial lining of the intestines. Similar tufted cells are found in the ... Also during worm infection the amount of tuft cells dramatically rises. Hyperplasia of tuft cells and goblet cells is a ...
"NK cell activation by dendritic cells is dependent on LFA-1-mediated induction of calcium-calmodulin kinase II: inhibition by ... "Evidence for direct protein kinase-C mediated modulation of N-methyl-D-aspartate receptor current". Mol. Pharmacol. 59 (5): 960 ... "Characterization and expression of multiple alternatively spliced transcripts of the Goodpasture antigen gene region. ... In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is ...
The spirochetes may also induce host cells to secrete quinolinic acid, which stimulates the NMDA receptor on nerve cells, which ... The CDC does not recommend urine antigen tests, PCR tests on urine, immunofluorescent staining for cell-wall-deficient forms of ... OspA antigens, shed by live Borrelia bacteria into urine, are a promising technique being studied. The use of nanotrap ... Within the tick midgut, the Borrelia's outer surface protein A (OspA) binds to the tick receptor for OspA, known as TROSPA. ...
In addition to GPCRs, arrestins bind to other classes of cell surface receptors and a variety of other signaling proteins. ... Arrestin-1 was originally identified as the S-antigen (SAG) causing uveitis (autoimmune eye disease), then independently ... Increased accessibility of these sites in receptor-bound arrestin targets the arrestin-receptor complex to the coated pit. ... Arrestin binding to the receptor blocks further G protein-mediated signaling and targets receptors for internalization, and ...
... and anti-acetylcholine receptor antibodies in myasthenia gravis". Tissue Antigens. 12 (5): 381-6. doi:10.1111/j.1399-0039.1978. ... In 1975, association with "HL-A1,8" (Current name: HLA A1-B8) was confirmed by serological typing of cells from myasthenics. ... "Correlation between acetylcholine receptor antibody titer and HLA-B8 and HLA-DRw3 antigens in myasthenia gravis". Trans Am ... An A1::DQ2 appears in India, however its major antigen genes superficially resemble European A1-B8 and it appears to be a ...
These cells include T cells, dendritic cells, macrophages, mast cells, basophils, eosinophils, epithelial cells and Paneth ... IL-25 has a heterodimeric receptor. The receptor is composed of two subunits IL-17RA and IL-17RB. The IL-17RA subunit is also ... promotes efficient protective immunity against Trichinella spiralis infection by enhancing the antigen-specific IL-9 response ... Th9 cells can arise not only from naive T cells but also from differentiated Th2 cells. Another function of IL-25 is the ...
A potential pathway for CD8+ T cell-mediated cytotoxicity in oral LP is described as follows: Antigens presented on MHC 1 ... El Tawdy A, Rashed L (July 2012). "Downregulation of TLR-7 receptor in hepatic and non-hepatic patients with lichen planus". ... An immune-mediated mechanism where basal keratinocytes are being targeted as foreign antigens by activated T cells, especially ... Chemokines are produced by activated CD8+ T cells that attract additional inflammatory cells, thereby promoting continued ...
UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of ... sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the ... the HIV-1 Tat protein and the 11S regulator subunit alpha is crucial for their effects on proteasome function including antigen ... Goff SP (Aug 2003). "Death by deamination: a novel host restriction system for HIV-1". Cell. 114 (3): 281-3. doi:10.1016/S0092- ...
IL-3 receptors can be found on a variety of cell types including many immature myelomonocytic cells in the hemopoietic system ... IL-3 is produced by T cells only after stimulation with antigens or other specific impulses. However, it was observed that IL-3 ... "Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors". Cell ... or that of other T cells (paracrine signaling) - both involve IL-2 binding to the IL-2 receptor on T cells (upregulated upon ...
T-cell antigen receptors: T-cell antigen receptors are found only on the cell membrane. For this reason, T-cell receptors were ... T-cell receptors consist of two polypeptide chains. The most… ... Other articles where T-cell antigen receptor is discussed: ... T-cell antigen receptors. T-cell antigen receptors are found only on the cell membrane. For this reason, T-cell receptors were ... www.britannica.com/science/T-cell-antigen-receptor", "title": "T-cell antigen receptor", "documentGroup": "TOPIC PAGINATED ...
... are synthetic proteins expressed on the surface of T cells. These receptors have both extracellular and intracellular ... a Structurally Differentiated Chimeric Antigen Receptor T (CAR-T) Cell Therapy Targeting B-Cell Maturation Antigen (BCMA), in ... Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017 Dec 28. 377 (26):2545-2554. [Medline]. [ ... Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017 Dec 28. 377 (26):2545-2554. [Medline]. ...
Cell. 2005 Aug 12;122(3):333-6. Research Support, N.I.H., Extramural; Research Support, Non-U.S. Govt; Research Support, U.S. ... Structures of many of the cell surface receptor-ligand complexes mediating the interactions between T cells and target cells ... How the T cell receptor sees antigen--a structural view.. Garcia KC1, Adams EJ. ... While snapshots of T cell receptors bound to their peptide-MHC ligands appear to have defined a general interaction or "docking ...
Antigen-specific T-cell activation independently of the MHC: chimeric antigen receptor-redirected T cells. Front Immunol. 2013; ... Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b. J Immunother ... Coexpressed catalase protects chimeric antigen receptor-redirected T cells as well as bystander cells from oxidative stress- ... Chimeric antigen receptor T cells against CD19 for multiple myeloma. N Engl J Med. 2015;373:1040-7.CrossRefPubMedPubMedCentral ...
Chimeric Antigen Receptor (CAR) T cell Immunotherapy- Competitive Landscape,... ... Chimeric Antigen Receptor (CAR) T cell Immunotherapy - Competitive Landscape, Pipeline and Market Analysis, 2017 Press Release ... DelveInsights, Chimeric Antigen Receptor (CAR) T cell Immunotherapy- Competitive Landscape, Pipeline and Market Analysis, 2017 ... Coverage of the Chimeric Antigen Receptor (CAR) T cell Immunotherapy pipeline on the basis of target, MOA, route of ...
Adoptive T-cell therapy of B-cell malignancies: conventional and physiological chimeric antigen receptors.. Liu L1, Sun M, Wang ... Adoptive T-cell therapy (ACT) using modified T cells with chimeric antigen receptors (CARs) targeted to specific tumor- ... Investigators optimized the design of CARs to enhance receptor mediated T cell signaling and demonstrated that second and third ... associated antigens expressed by B-cell malignancies represents an attractive approach for cancer immunotherapy. ...
Genomic organization of the human T-cell antigen-receptor alpha/delta locus. K Satyanarayana, S Hata, P Devlin, M G Roncarolo, ... Two clusters of overlapping cosmid clones comprising about 100 kilobases (kb) at the human T-cell antigen-receptor alpha/delta ... Genomic organization of the human T-cell antigen-receptor alpha/delta locus ... Genomic organization of the human T-cell antigen-receptor alpha/delta locus ...
T cell Immunotherapy - Competitive Landscape, Pipeline and Market Analysis, 2017 provides information on pricing,... ... Chimeric Antigen Receptor (CAR) T cell Immunotherapy Pipeline on the Basis of Target, MOA, Route of Administration, Technology ... DelveInsights, Chimeric Antigen Receptor (CAR) T cell Immunotherapy- Competitive Landscape, Pipeline and Market Analysis, 2017 ... Coverage of the Chimeric Antigen Receptor (CAR) T cell Immunotherapy pipeline on the basis of target, MOA, route of ...
However, in competition experiments only the high-affinity B cells responded to antigen. CD19 deficiency increased the affinity ... large differences in affinity produce only small differences in the intrinsic ability of B cells to respond to antigen, and ... and low-affinity B cells to NP-Ficoll was only twofold. ... Lyn deficiency enhanced clonal expansion but abrogated B cell ... To examine how B cell receptor affinity affects clonal selection in thymus-independent type 2 (TI-2) immune responses, we ...
... engagement leads to actin polymerization at the site of T cell contact with antigen-presenting cells. Here we have studied the ... were recruited to the TCR during initial T cell activation, where they colocalized with the tyrosine kinase Zap70. The ... dynamic activity of proteins involved in regulating actin polymerization in live T cells after activation. Two such adaptor ... T cell receptor (TCR) engagement leads to actin polymerization at the site of T cell contact with antigen-presenting cells. ...
T-cell antigen receptor binding sites for the microbial superantigen staphylococcal enterotoxin A.. C H Pontzer, M J Irwin, N R ... T-cell antigen receptor binding sites for the microbial superantigen staphylococcal enterotoxin A. ... T-cell antigen receptor binding sites for the microbial superantigen staphylococcal enterotoxin A. ... T-cell antigen receptor binding sites for the microbial superantigen staphylococcal enterotoxin A. ...
The successful use of chimeric antigen receptors (CARs) for the generation of antigen-specific effector T cells suggests that a ... Current methods to generate alloantigen-specific Tregs rely on expansion with allogeneic antigen-presenting cells, which ... disease-relevant antigen-specific Tregs may have numerous advantages, such as a need for fewer cells and reduced risk of ... Adoptive immunotherapy with regulatory T cells (Tregs) is a promising treatment for allograft rejection and graft-versus-host ...
... cell-based therapy for B-cell malignancies, and early phase clinical trials have been launched in recent years. The few ... Many studies have struggled to improve the clinical responses to and benefits of CART-cell treatment of solid tumors. In this ... Although antitumor effects were confirmed,i, in vitro,/i, and in animal models, CART-cell-based therapy still faces several ... Importantly, we will suggest improvements that could increase the therapeutic effectiveness of CART cells for solid tumors and ...
... each B lymphocyte contains up to 120000 B cell antigen receptor (BCR) complexes on its cell surface. How these abundant ... receptors remain silent on resting B cells and how they can be activated by a molecularly diverse set of ligands is poorly ... To detect its cognate antigen, each B lymphocyte contains up to 120000 B cell antigen receptor (BCR) complexes on its cell ... The dissociation activation model of B cell antigen receptor triggering FEBS Lett. 2010 Dec 15;584(24):4872-7. doi: 10.1016/j. ...
... including B-cell maturation antigen (BCMA), CD38, CD138, SLAMF7, and natural killer gro... more ... Several myeloma target antigens are being investigated in clinical trials of patients with R/R multiple myeloma, ... a Structurally Differentiated Chimeric Antigen Receptor T (CAR-T) Cell Therapy Targeting B-Cell Maturation Antigen (BCMA), in ... Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017 Dec 28. 377 (26):2545-2554. [Medline]. [ ...
... is a nuclear receptor acting as a transcription factor involved in the regulation of energy metabolism, cell cycle, cell ... Beyond CAR-T cells: Natural killer cells immunotherapy.. Authors: Corral Sánchez MD, Fernández Casanova L, Pérez-Martínez A ... Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ ... Curing Ph+ ALL: assessing the relative contributions of chemotherapy, TKIs, and allogeneic stem cell transplant. ...
T-cell immunotherapy has gained significant attention in the past decade due to its considerable potential in the treatment of ... Fluorescent antigen-transfected target cell cytotoxic T lymphocyte assay for ex vivo detection of antigen-specific cell- ... Chimeric antigen receptor (CAR) T cell therapy for malignant cancers: summary and perspective. J Cell Immunother. 2016;2(2):59- ... Chimeric antigen receptor T cells for cancer immunotherapy. J Clin Oncol. 2015;33(15):1703-6.CrossRefGoogle Scholar ...
The advent of CAR T‐cell therapy has seen significant improvements in survival and is a potential cure for patients with ...
... and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell ... and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell ... Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in ... Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in ...
... 02.09.2015 ... tumor cells but not of CD30+ healthy cells like hematopoietic stem cells. Specific genetic modifications of the anti-CD30 CAR ... This approach has been tested in vitro with CD30+ hematopoietic stem cells and CD30+ tumor cells and in vivo in mice ... Im Focus: Stem cell divisions in the adult brain seen for the first time. Scientists from the University of Zurich have ...
... chimeric T cell receptors or artificial T cell receptors) are receptor proteins that have been engineered to give T cells the ... Chimeric antigen receptor T cells (also known as CAR T cells) are T cells that have been genetically engineered to produce an ... Dual-antigen receptor: CAR-T cells are engineered to express two tumor-associated antigen receptors at the same time, reducing ... The intracellular T-cell signaling domain lies in the receptors endodomain, inside the cell. After an antigen is bound to the ...
... a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, after myeloablative ... A patient with refractory multiple myeloma received an infusion of CTL019 cells, ... Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma N Engl J Med. 2015 Sep 10;373(11):1040-7. doi: 10.1056/ ... a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, after myeloablative ...
... and thus of the B-cell repertoire, is the result of very complex immunogenetic mechanisms. So, this chapter gives a brief ... T-cells during antigen priming by dendritic cells in T-cell zones [46] (comment in [47]). The Tfh cells then give survival and ... B-cell antigen receptor complex, DZ: dark zone, FDC: follicular dendritic cell, LZ: light zone, M: mantle zone, SHM: somatic ... after both T-cells and B-cells have been primed with antigen. The activated B-cells follow one of the following two fates to ...
In this blog, read about adoptive cell transfer, the process of training and expanding a patients own immune cells and placing ... Immunotherapy is a groundbreaking option because it can hypothetically target cancer cells specifically while leaving healthy ... cells intact, which can decrease the number of adverse effects associated with current treatment options. ... it back into the patient to fight the cancer with their own cells. ...
... antigens and antibodies, polypeptide hormones, and small molecules. [Roland F Beers; Edward G Bassett; Miles Laboratories.;] ... Cell receptors schema:about cell_receptors> ; # Cell receptors ... Cell receptors a schema:Intangible ;. schema:name "Cell receptors"@en ;. . ... Cell membrane receptors for viruses, antigens and antibodies, polypeptide hormones, and small molecules. Author:. Roland F ...
Viral vectors have been used to genetically modify in vitro expanded NK cells to express chimeric antigen receptors (CARs), ... A K562 cell line expressing high levels of anti-CD19 CARs was generated as a donor cell to transfer the anti-CD19 CARs onto NK ... Anti-CD19 CAR expression was observed in expanded NK cells after these cells were co-cultured for one hour with freeze/thaw- ... Acquisition of anti-CD19 CARs via trogocytosis enhanced NK cell-mediated cytotoxicity against the B-cell acute lymphoblastic ...
... both RP215 and antibodies against antigen-receptors were shown to affect more than a dozen of genes involved in cell ... which consisted mainly of these cancer cell-expressed antigen receptors. Experimental evidence has clearly indicated that ... were also found to be highly regulated by both RP215 and anti-antigen receptor antibodies. For example, RP215 and anti-antigen ... including immunoglobulins and T-cell receptors, are known to be widely expressed by cancer cells through unconfirmed mechanisms ...
Engineering γδT cells limits tonic signaling associated with chimeric antigen receptors. *View ORCID ProfileJonathan Fisher1,2 ... Engineering γδT cells limits tonic signaling associated with chimeric antigen receptors. By Jonathan Fisher, Roshan Sharma, ... Engineering γδT cells limits tonic signaling associated with chimeric antigen receptors. By Jonathan Fisher, Roshan Sharma, ... Engineering γδT cells limits tonic signaling associated with chimeric antigen receptors Message Subject. (Your Name) has ...
... cells expressing polyclonal repertoire of endogenous γδ T-cell receptors and introduced CD19-specific chimeric antigen receptor ... T-cell receptor ligation induces distinct signaling pathways in naïve vs. antigen-experienced T cells. Proc. Natl. Acad. Sci. U ... Tonic 4-1BB costimulation in chimeric antigen receptors impedes T cell survival and is vector-dependent. Cell Rep. 21, 17-26 ( ... Human T cell receptor γδ cells recognize endogenous mevalonate metabolites in tumor cells. J. Exp. Med. 197, 163-168 (2003).. ...
The interaction of the T cell receptor for antigen (TCR) with its antigen-major histocompatibility complex ligand is difficult ... Expression of T cell antigen receptor heterodimers in a lipid-linked form ... Expression of T cell antigen receptor heterodimers in a lipid-linked form ... Expression of T cell antigen receptor heterodimers in a lipid-linked form ...
  • DelveInsights, Chimeric Antigen Receptor (CAR) T cell Immunotherapy - Competitive Landscape, Pipeline and Market Analysis, 2017, report provides comprehensive insights about marketed and pipeline drugs across this Mechanism of action. (mynewsdesk.com)
  • Key objective of the report is to establish the understanding for all the marketed and pipeline drugs that fall under Chimeric Antigen Receptor (CAR) T cell Immunotherapy. (mynewsdesk.com)
  • This report provides information on the therapeutic development based on Chimeric Antigen Receptor (CAR) T cell Immunotherapy mechanism of action dealing with around 20+ active pipeline drugs. (mynewsdesk.com)
  • DelveInsights Report also assesses the Chimeric Antigen Receptor (CAR) T cell Immunotherapy therapeutics by Monotherapy, Combination products, Molecule type and Route of Administration. (mynewsdesk.com)
  • Adoptive T-cell therapy (ACT) using modified T cells with chimeric antigen receptors (CARs) targeted to specific tumor-associated antigens expressed by B-cell malignancies represents an attractive approach for cancer immunotherapy. (nih.gov)
  • Adoptive immunotherapy with regulatory T cells (Tregs) is a promising treatment for allograft rejection and graft-versus-host disease (GVHD). (jci.org)
  • The outcome is equally as good as for Ph- disease, and with targeted tyrosine kinase inhibitor therapies in addition to chemotherapy, the novel immunotherapy approaches, and the extension of allogeneic hematopoietic stem cell transplant (allo-HCT) to older individuals, there is the potential to exceed this outcome. (medworm.com)
  • Chimeric antigen receptor (CAR) T-cell immunotherapy has gained significant attention in the past decade due to its considerable potential in the treatment of various types of malignancies, particularly hematological. (springer.com)
  • Chimeric antigen receptor T cells for cancer immunotherapy. (springer.com)
  • Hombach A, Hombach AA, Abken H. Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc 'spacer' domain in the extracellular moiety of chimeric antigen receptors avoids 'off-target' activation and unintended initiation of an innate immune response. (springer.com)
  • Adoptive cellular immunotherapy (ACT) employing engineered T lymphocytes expressing chimeric antigen receptors (CARs) has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. (frontiersin.org)
  • One approach to cancer immunotherapy entails genetically engineering a patient's T cells to express chimeric antigen receptors (CARs) that recognize and attack tumor cells. (frontiersin.org)
  • Natural killer (NK) cells have the capacity to target tumors and are ideal candidates for immunotherapy. (plos.org)
  • In this study, we used trogocytosis as a non-viral method to modify NK cells for immunotherapy. (plos.org)
  • Natural killer (NK) cells have the ability to recognize and eliminate tumor cells, making them ideal candidates for tumor immunotherapy [1] , [2] . (plos.org)
  • CD19 is an ideal target antigen for immunotherapy because it is expressed on nearly all leukemia cells in most patients with B-cell acute lymphoblastic leukemia (ALL) and chronic lymphoblastic leukemia (CLL) [13] , [14] . (plos.org)
  • The in vitro generation of T cells with defined antigen specificity by T cell receptor (TCR) gene transfer is an established method to create cells for immunotherapy. (mdc-berlin.de)
  • CAR T-cell therapy is a rapidly emerging adoptive cell transfer immunotherapy for select patients with relapsed or refractory cancers. (cms.gov)
  • We list other attractive potential targets for CAR T cell therapy for MPM, and discuss augmentation strategies of CAR T cell therapy with other forms of immunotherapy in this disease. (mdpi.com)
  • Adoptive transfer of T cells engineered to express a chimeric antigen receptor (CAR) has emerged as a powerful targeted immunotherapy, showing striking responses in highly refractory populations. (bloodjournal.org)
  • Chimeric antigen receptor T cells (also known as CAR T cells) are T cells that have been genetically engineered to produce an artificial T-cell receptor for use in immunotherapy. (wikipedia.org)
  • The premise of CAR-T immunotherapy is to modify T cells to recognize cancer cells in order to more effectively target and destroy them. (wikipedia.org)
  • These NK-CAR-iPSC-NK cells now provide standardized, targeted 'off-the-shelf' lymphocytes for anti-cancer immunotherapy. (ca.gov)
  • CAR T-cell therapy is one of a group of new treatments, called immunotherapy, that harnesses the power of the body's immune system to detect and destroy cancer cells. (berkeleywellness.com)
  • In this review, we summarize the clinical results for CAR T cells in the case of hematologic and solid tumors, along with the current developments in CAR T cell immunotherapy. (eurekaselect.com)
  • Feng Li, Tengfei Zhang, Ling Cao and Yi Zhang*, "Chimeric Antigen Receptor T Cell Based Immunotherapy for Cancer", Current Stem Cell Research & Therapy (2018) 13: 327. (eurekaselect.com)
  • In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. (springer.com)
  • Rizvi NA, Peters S. Immunotherapy for unresectable stage III nonsmall- cell lung cancer. (springer.com)
  • This new type of targeted immunotherapy merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity and long-term persistence provided by cytotoxic T cells. (springermedizin.de)
  • Novel natural killer (NK) cell-directed strategies in cancer immunotherapy aim at specifically modulating the balance between NK cell receptor signals toward tumor-specific activation. (aacrjournals.org)
  • Antigen-specific 2B4ζ-expressing NK cells may be a powerful new tool for adoptive immunotherapy of leukemia and other malignancies. (aacrjournals.org)
  • In recent years, natural killer (NK) cell strategies for cancer immunotherapy have stimulated increasing interest but their clinical application has largely been restricted to the haploidentical hematopoietic stem cell transplantation setting, where natural killer immunoglobulin receptor mismatches between the donor and recipient are exploited to enhance the graft-antileukemia effect. (aacrjournals.org)
  • Adoptive cellular immunotherapy with anti CD 19 chimeric antigen receptor (CAR) T cell has changed the treatment landscape in B cell lymphomas. (medworm.com)
  • A promising and expensive type of immunotherapy, called CAR T-cell therapy, is now covered by Medicare. (medworm.com)
  • The U.S. Food and Drug Administration has approved the immunotherapy procedure for non-Hodgkin lymphoma and B-cell precursor acute lymphoblastic leukemia. (medworm.com)
  • Adoptive immunotherapy with chimeric antigen receptor (CAR)-engineered T (CART) cells can target and kill malignant cells, thereby inducing durable clinical responses in hematopoietic malignancies ( 1-3 ). (aacrjournals.org)
  • T cells infiltrating tumors have alterations in signal transduction and function (1 , 2) , which may impair the therapeutic efficacy of various forms of immunotherapy. (aacrjournals.org)
  • Recently, a new form of immunotherapy using genetically engineered chimeric antigen receptor (CAR) T-cells has been developed. (pulsus.com)
  • CD19 CAR T cell-redirected immunotherapy is an attractive option for patients with various CD19+ leukemias (e.g. (pulsus.com)
  • Its significant efficacy coupled with limited toxicities makes CD19 CAR T-cell immunotherapy an ideal treatment approach for ALL and NHL. (pulsus.com)
  • Chimeric antigen receptor (CAR) T-cell immunotherapy has revolutionized the treatment of refractory leukemias and lymphomas, but is associated with significant toxicities, namely cytokine release syndrome (CRS) and neurotoxicity. (aacrjournals.org)
  • An autologous form of cellular immunotherapy - chimeric antigen receptor (CAR) T-cell therapy - is currently under investigation. (lymphomacoalition.org)
  • There are a number of immunotherapy approaches but this article will focus on CART T-cell therapy specifically. (lymphomacoalition.org)
  • Technology could be useful for development of immunotherapy against cancer cells that lost MHC class I or MHC class I antigen presentation machinery. (roswellpark.org)
  • Adoptive T cell immunotherapy has shown promise in treating some cancers, but the challenge of isolating T cells with high avidity for tumor antigens limits large-scale applicability. (washington.edu)
  • Using a well-characterized murine model of adoptive T cell immunotherapy for established malignancy, we have demonstrated the feasibility of eliminating disseminated leukemia using T cells genetically modified by TCR gene transfer.We next examined the potential of targeting a clinically relevant tumor antigen, the transcription factor WT1, for which the expression patterns in normal and malignant cells are similar in mouse and man. (washington.edu)
  • it recognizes a specific protein on the surface of malignant cells (eg, CD19 on B-cells). (medscape.com)
  • CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. (medscape.com)
  • The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells. (medscape.com)
  • Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy. (medscape.com)
  • Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. (medscape.com)
  • Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. (medscape.com)
  • End of phase I results of ZUMA-3, a phase 1/2 study of KTE-X19, anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in adult patients (pts) with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). (medscape.com)
  • CD19 deficiency increased the affinity threshold of TI-2 responses, whereas Lyn deficiency enhanced clonal expansion but abrogated B cell terminal differentiation. (nature.com)
  • For example, several groups have reported clinical trials with anti-CD19 CART cells in which favorable clinical efficacy resulted from the specific recognition and eradication of CD19-positive tumor cells [ 3 , 4 , 6 ]. (hindawi.com)
  • A patient with refractory multiple myeloma received an infusion of CTL019 cells, a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, after myeloablative chemotherapy (melphalan, 140 mg per square meter of body-surface area) and autologous stem-cell transplantation. (nih.gov)
  • This response was achieved despite the absence of CD19 expression in 99.95% of the patient's neoplastic plasma cells. (nih.gov)
  • One example is ALL, acute lymphoblastic leukemia, where CAR T cells engineered to target CD19, a major B cell maker, were able to wipeout cancer in 90% of the patients treated in that study 1 . (biolegend.com)
  • A K562 cell line expressing high levels of anti-CD19 CARs was generated as a donor cell to transfer the anti-CD19 CARs onto NK cells via trogocytosis. (plos.org)
  • Anti-CD19 CAR expression was observed in expanded NK cells after these cells were co-cultured for one hour with freeze/thaw-treated donor cells expressing anti-CD19 CARs. (plos.org)
  • Immunofluorescence analysis confirmed the localization of the anti-CD19 CARs on the NK cell surface. (plos.org)
  • Acquisition of anti-CD19 CARs via trogocytosis enhanced NK cell-mediated cytotoxicity against the B-cell acute lymphoblastic leukemia (B-ALL) cell lines and primary B-ALL cells derived from patients. (plos.org)
  • Further, expression of anti-CD19 chimeric antigen receptors (CARs) containing 41BB and CD3ζ signal domains on NK cells enhanced the activating signals originating from CD19 antigen engagement, leading to cytotoxicity specifically against B-cell leukemia [4] . (plos.org)
  • CD19-targeting therapies employing chimeric antigen receptor (CAR) T cells are a breakthrough in cancer therapy. (mdpi.com)
  • Complete remission (CR) rates as high as 90% have been reported in children and adults with relapsed and refractory ALL treated with CAR-modified T cells targeting the B-cell-specific antigen CD19. (bloodjournal.org)
  • Chimeric antigen receptor (CAR)-modified T cells targeting CD19, the best-studied CAR T-cell therapy to date, will be discussed, with a focus on clinical trials for ALL demonstrating efficacy as well as toxicity and toxicity management. (bloodjournal.org)
  • Clinical trials in the early 2010s using second generation CARs targeting CD19, a protein expressed by normal B cells as well as B cell leukemias and lympohomas, by investigators at the NCI, University of Pennsylvania, and Memorial Sloan Kettering Cancer Center demonstrated the clinical efficacy of CAR T cell therapies and resulted in complete remissions in many heavily pre-treated patients. (wikipedia.org)
  • Patients with relapsed or refractory CD19-positive cancers experienced complete responses with no major side effects following treatment with CAR-NK cell therapy. (curetoday.com)
  • Patients with relapsed or refractory CD19-positive cancers who were treated with cord blood-derived chimeric antigen receptor (CAR) natural killer (NK)-cell therapy experienced responses without the development of major toxic effects, according to a phase 1/2 trial published in The New England Journal of Medicine . (curetoday.com)
  • The researchers genetically engineered the cells to recognize CD19, a cancer-specific target, and are reinforced with an immune signaling molecule, IL-15, that enhances the multiplication and survival of the NK cells. (curetoday.com)
  • Cherukuri A, Cheng PC, Pierce SK (2001a) The role of the CD19/CD21 complex in B-cell processing and presentation of complement-tagged antigens. (springer.com)
  • Cherukuri A, Cheng P, Sohn H, Pierce S (2001b) The CD19/CD21 complex functions to prolong B-cell antigen receptor signaling from lipid rafts. (springer.com)
  • A single-cell analysis of the preinfusion CD19 CAR product from patients with NHL demonstrated that CAR products contain polyfunctional T-cell subsets capable of deploying multiple immune programs represented by cytokines and chemokines including interferon-γ (IFN-γ), IL-17A, IL-8, and macrophage inflammatory protein 1-α. (bloodjournal.org)
  • Additionally, treatment of solid tumors with CAR-T cells has been less successful than targeting CD19-expressing tumors. (ca.gov)
  • The primary objective of this study is to determine the ability to take a patient's own cells (T lymphocytes) and grow them in the laboratory with the CD19/CD22-CAR receptor gene through a process called 'lentiviral transduction (also considered gene therapy) and growing them to large numbers to use as a treatment for hematologic cancers in children and young adults. (centerwatch.com)
  • Researchers want to see if giving modified CD19/CD22-CAR T cells to people with these cancers can attack cancer cells. (centerwatch.com)
  • To study the safety and effects of giving CD19/CD22-CAR T cells to children and young adults with B-cell cancer. (centerwatch.com)
  • Assess the safety of administering escalating doses of autologous CD19/CD22-CAR engineered T cells that meet established release specifications in children and young adults with CD19+CD22+ B cell ALL or lymphoma following a cyclophosphamide/fludarabine conditioning regimen. (centerwatch.com)
  • Patients will receive a lymphodepleting preparative regimen of fludarabine (25 mg/m^2/d x 3 on Days -4, -3, -2) and cyclophosphamide (900 mg/m^2/d x 1 on Day -2) followed by infusion of CD19/CD22-CAR T-cells on D0. (centerwatch.com)
  • Patients who are CAR pre-treated (with exception for those with an interval HSCT) will receive increased lymphodepleting preparative regimen of fludarabine (30 mg/m^2/d x 4 on Days -5, -4, -3, -2) and cyclophosphamide (600 mg/m^2/d x 2 on Days -3, -2) followed by infusion of CD19/CD22-CAR T-cells on D0. (centerwatch.com)
  • CD19 is extensively expressed on cancerous cells in B cell malignancies. (eurekaselect.com)
  • We have combined a robust T cell culture system 6 with lentiviral vector transduction of human T cells to express a CD19-specific CAR (CART-19 cells). (jcancer.org)
  • In vitro -stimulated NK cells from healthy donors and pediatric leukemia patients were gene modified with CD19 or G D2 -specific chimeric receptors containing either the T-cell receptor ζ or 2B4 endodomain alone or combined. (aacrjournals.org)
  • Typically, engineered CAR T-cells recognize CD19 specifically, a universal B-cell surface marker expressed in many forms of B-cell malignancies. (pulsus.com)
  • In fact, anti-CD19 CAR T-cell therapy has shown remarkable clinical efficacy in the treatment of these patients. (pulsus.com)
  • This review summarizes recent developments in the field of CAR T cell therapy with an emphasis on the utilization of various CD19 CAR T cell constructs in the clinical treatment of NHL and ALL. (pulsus.com)
  • These cells are engineered to react against CD19 which is on the surface of B cells. (lymphomacoalition.org)
  • The white blood cells along with the T cells are then sent to a laboratory where they are genetically modified or manipulated to react against CD19. (lymphomacoalition.org)
  • Once the reprogrammed T cells are infused into the patient's body, they expand and start looking for cancer cells that express CD19. (lymphomacoalition.org)
  • Once found, the reprogrammed T cells attach to the CD19-expressing cells and start to kill them. (lymphomacoalition.org)
  • One such agent is CTL019, a CAR-modified T-cell therapy that reacts against CD19. (lymphomacoalition.org)
  • Recently, chimeric antigen receptor (CAR) T cell therapy has shown promising results in hematological tumors and current research is going on in various solid tumors like ovarian cancer. (springer.com)
  • The few published clinical studies of CART cells in solid tumors have addressed safety and feasibility, but the clinical outcome data are limited. (hindawi.com)
  • Although antitumor effects were confirmed in vitro and in animal models, CART-cell-based therapy still faces several challenges when directed towards solid tumors, and it has been difficult to achieve the desired outcomes in clinical practice. (hindawi.com)
  • Many studies have struggled to improve the clinical responses to and benefits of CART-cell treatment of solid tumors. (hindawi.com)
  • In this review, the status quo of CART cells and their clinical applications for solid tumors will be summarized first. (hindawi.com)
  • Importantly, we will suggest improvements that could increase the therapeutic effectiveness of CART cells for solid tumors and their future clinical applications. (hindawi.com)
  • These interventions will make treatment with CART cells an effective and routine therapy for solid tumors. (hindawi.com)
  • The clinical studies of CART cells for solid tumors have begun recently. (hindawi.com)
  • Up to date, eleven studies of CART-cell therapy for solid tumors have been conducted in the past decade (Table 1 ), and thirty-five clinical trials for various solid tumors are listed at ClinicalTrials.gov ( http://www.clinicaltrials.gov ) (Figure 1 ). (hindawi.com)
  • The registered numbers of clinical trials increase annually, and a range of tumor antigens, including CEA, mesothelin, HER2, and GD2, are being targeted for various solid tumors. (hindawi.com)
  • Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. (frontiersin.org)
  • Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. (frontiersin.org)
  • The recognition specificity of different non-self-antigens or defective self-antigens (tumors) by a well-defined B-cell clone does not result from the presence of an extensive number of receptor genes, but rather from immunogenetic mechanisms affecting a limited number of IG genes, including mechanisms of genetic recombination, mutations, deletions or insertions, and gene repair, through very complex regulatory mechanisms that are responsible for a large B-cell repertoire. (intechopen.com)
  • It was also discovered that chemotherapy and immunosuppression prior to ACT increased efficacy in these transfers, not only because of the two-pronged treatment of tumors, but also because of the elimination of old immune cells that were no longer effective at destroying tumor cells. (biolegend.com)
  • So far, many of the most promising results using CAR-transfected ACT have been observed in liquid tumors, where the cancer does not originate from a specific location, but instead a single cell type throughout the blood. (biolegend.com)
  • Viral vectors have been used to genetically modify in vitro expanded NK cells to express chimeric antigen receptors (CARs), which confer cytotoxicity against tumors. (plos.org)
  • This novel strategy could be a potential valuable therapeutic approach for the treatment of B-cell tumors. (plos.org)
  • We have previously genetically modified in vitro expanded NK cells to express DAP10 and the chimeric NKG2D receptor containing the CD3ζ signal domain, which altered the balance between the activating and inhibitory signals of NK cells and enhanced the cytotoxicity against NKG2D ligand-bearing tumors [3] . (plos.org)
  • Despite the benefits of chimeric antigen receptor (CAR)-T cell therapies against lymphoid malignancies, responses in solid tumors have been more limited and off-target toxicities have been more marked. (sciencemag.org)
  • Adoptive transfer of T cell receptor-engineered (TCR-engineered) T cells is a promising approach in cancer therapy but needs improvement for more effective treatment of solid tumors. (jci.org)
  • In addition to checkpoint blockade, adoptive T cell transfer (ACT) using chimeric antigen receptors (CARs) has shown impressive clinical outcomes in leukemias and is now being explored in solid tumors. (mdpi.com)
  • Scientists harvest T cells from people, genetically alter them, then infuse the resulting CAR-T cells into patients to attack their tumors. (wikipedia.org)
  • Once isolated from a person, these T cells are genetically engineered to express a specific CAR, which programs them to target an antigen that is present on the surface of tumors. (wikipedia.org)
  • Similar early clinical trials of CAR T cells in solid tumors in the 1990s using first generation CARs targeting a solid tumor antigens such as MUC1 did not show long term persistence of the transferred T cells or result in significant remissions. (wikipedia.org)
  • Tests of all treated patients showed that their normal B cells had been killed along with the tumors. (fightaging.org)
  • This mechanism is efficiently counteracted in many human tumors, where cells evade NK cell-mediated killing by shedding or intracellular retention of ligands for activating receptors ( 8 ). (aacrjournals.org)
  • Target-mediated toxicity is a major limitation in the development of chimeric antigen T-cell receptors (CAR) for adoptive cell therapy of solid tumors. (aacrjournals.org)
  • The use of affinity-tuned scFvs offers a strategy to empower wider use of CAR T cells against validated targets widely overexpressed on solid tumors, including those considered undruggable by this approach. (aacrjournals.org)
  • T cells infiltrating tumors have a decreased expression of signal transduction proteins, a diminished ability to proliferate, and a decreased production of cytokines. (aacrjournals.org)
  • These CAR-T cells will recognize a molecular marker on the surface of glioma cancer stem cells and kill the tumors. (ca.gov)
  • Like many tumor-associated antigens, generating robust immune responses to the WT1 protein has been difficult as endogenous WT1 expression may delete or render anergic most of the high avidity T cell repertoire capable of recognizing WT1 expressing tumors. (washington.edu)
  • However, none of the T cells isolated recognized murine tumors endogenously expressing WT1. (washington.edu)
  • We also isolated two human T cell clones specific for WT1RMFPNAPYL, one of which recognizes human tumors expressing this antigen. (washington.edu)
  • When expressed by a T cell, CARs confer antigen specificity determined by the targeting domain ( 1 , 2 ). (frontiersin.org)
  • 2003) Human epithelial cancers secrete immunoglobulin G with unidentified specificity to promote growth and survival of tumor cells. (scirp.org)
  • Christensen S, Shupe J, Nickerson K, Kashgarian M, Flavell R, Shlomchik M (2006) Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. (springer.com)
  • Specificity studies involving A and cogenic A/θAKR mice clearly demonstrated that the cell surface fluorescence and cytotoxicity produced by the antiserum is directed solely toward the θAKR alloantigen. (rupress.org)
  • Here, we show that in the antibody-mediated autoimmune disease pemphigus vulgaris (PV), autoantigen-based chimeric immunoreceptors can direct T cells to kill autoreactive B lymphocytes through the specificity of the B cell receptor (BCR). (sciencemag.org)
  • Gene transfer techniques have now been developed to genetically modify T cells to confer novel antigen specificity by stably expressing a chimeric antigen receptor (CAR) on their surface. (jcancer.org)
  • This allows the immune cells to recognize and attack cancer cells with a high degree of specificity, and the early results in the trial were impressive . (fightaging.org)
  • Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibodytype specificity. (springer.com)
  • Integration of the 2B4 endodomain into T-cell receptor ζ chimeric receptors significantly enhanced all aspects of the NK cell activation response to antigen-expressing leukemia or neuroblastoma cells, including CD25 up-regulation, secretion of IFN-γ and tumor necrosis factor-α, release of cytolytic granules, and growth inhibition, and overcame NK cell resistance of autologous leukemia cells while maintaining antigen specificity. (aacrjournals.org)
  • HLA, human leukocyte antigen. (cdc.gov)
  • After proteasomal processing, the PRAME300-309 peptide ALYVDSLFFL (ALY) is presented in the context of human leukocyte antigen HLA-A*02:01 molecules for recognition by the T cell receptor (TCR) of cytotoxic T cells. (sigmaaldrich.com)
  • Maternal killer-cell immunoglobulin-like receptors and paternal human leukocyte antigen ligands in recurrent pregnancy loss cases in Turkey. (physiciansweekly.com)
  • Compatibility between partners for human leukocyte antigen (HLA) genotypes and the relationships between maternal killer-cell immunoglobulin-like receptor (KIR) and paternal HLA-Bw4/Bw6 and HLA-C1/C2 supra-groups were investigated in 25 couples with RPL in comparison to healthy couples with children. (physiciansweekly.com)
  • Authors: Mrowka P, Glodkowska-Mrowka E Abstract Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor acting as a transcription factor involved in the regulation of energy metabolism, cell cycle, cell differentiation, and apoptosis. (medworm.com)
  • Authors: Schultz L, Gardner R Abstract Immunotherapies have been successfully developed for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) with FDA approval of blinatumomab, inotuzumab, and tisagenlecleucel for relapsed or refractory patients. (medworm.com)
  • While snapshots of T cell receptors bound to their peptide-MHC ligands appear to have defined a general interaction or "docking" solution, many of the most fundamental structural questions in antigen recognition lack detailed answers and thus pose exciting experimental challenges for the future. (nih.gov)
  • Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T cells. (springer.com)
  • NY-ESO-1-reactive TCRs from the mice showed superior recognition of tumor cells and higher functional activity compared with TCRs from humans. (jci.org)
  • These engineered cells have the ability to identify antigens in a major histocompatibility complex (MHC)-independent manner, unlike unmodified T cells that require T cell receptor (TCR)-mediated antigen recognition. (urotoday.com)
  • CARs combine an antigen recognition domain of a specific antibody with an intracellular domain of the CD3-zeta chain or FcγRI protein into a single chimeric protein 1 . (jcancer.org)
  • CAR is an artificial antigen receptor that mediates antibody-targeted recognition. (springermedizin.de)
  • The specific recognition systems are the antibodies, capable of recognizing antigens in solution and the T lymphocytes equipped with T-cell antigen receptors (TCR) capable of recognizing internal antigens associated with the antigens of the major histocompatibility complex. (thefreedictionary.com)
  • CAR T cells trigger apoptosis in tumor targets in an MHCindependent manner upon recognition and ligation to a specific tumor associated antigen (TAA). (pulsus.com)
  • Because of their different abilities in direct recognition of cancer cells, these two types of CD4+ T cells (TR-CD4 and NTR- CD4) are considered to play different roles at the local tumor site, i.e. (roswellpark.org)
  • TR-CD4 efficiently provide CD4-help by direct recognition of cancer cells. (roswellpark.org)
  • This invention takes advantage of the fact that TR-CD4 cells provide CD4 help by direct recognition of cancer cells by using this function to provide TCR polypeptides and recombinant polynucleotides encoding them for use in novel prophylactic and/or therapeutic treatment modalities and compositions. (roswellpark.org)
  • Roswell Park Comprehensive Cancer Center is seeking partners to help co-develop compositions and methods for prophylaxis and/or therapy of cancers using T cells that have been engineered to be capable of direct recognition of tumor antigen and MHC class II expressing cancer cells. (roswellpark.org)
  • New method especially important to generate CD4+ T cells that provide efficient "CD4 help" at the local tumor site without the requirement of antigen presenting cells via direct recognition of cancer cells. (roswellpark.org)
  • We hypothesized that in vitro engineering to increase TCR affinity would improve tumor cell recognition, although the potential for such high affinity TCRs to recognize normal tissues expressing low levels of WT1 would need to be assessed.To test this hypothesis, we characterized the murine and human T cell responses elicited to WT1RMFPNAPYL. (washington.edu)
  • The TCRs from these T cells are being used as templates for in vitro mutagenesis and selection of higher affinity TCRs by yeast display to determine the threshold required for efficient tumor recognition without targeting normal tissues. (washington.edu)
  • CDR4 of the β-chain is not thought to participate in antigen recognition, but has been shown to interact with superantigens. (wikipedia.org)
  • In contrast to conventional T cell receptors (TCRs), which recognize antigens in a major histocompatibility complex (MHC)-dependent manner, CARs can potentially redirect the effector functions of a T cell toward any protein or non-protein target expressed on the cell surface. (frontiersin.org)
  • Similar to T-cell receptors (TCRs), functional genes of immunoglobulins (Igs) are the result of somatic recombination of DNA containing the relatively limited germinal genetic information, using the so-called V(D)J recombination process that occurs between individual genes (also referred to as gene segments) of the variable domains of the H and L chains (or α, β, γ, and δ chains of TCRs). (intechopen.com)
  • Regarding shared (self) tumor antigens, it is unclear whether the human CD4+ T cell repertoire has been shaped by tolerance mechanisms and lacks highly functional TCRs suitable for therapy. (jci.org)
  • Here, TCRs against the tumor-associated antigen NY-ESO-1 were isolated either from human CD4+ T cells or from mice that express a diverse human TCR repertoire with HLA-DRA/DRB1*0401 restriction and are NY-ESO-1 negative. (jci.org)
  • These data suggest that MHC II-restricted TCRs against NY-ESO-1 from a nontolerant nonhuman host are of optimal affinity and that the combined use of MHC I- and II-restricted TCRs against NY-ESO-1 can make adoptive T cell therapy more effective. (jci.org)
  • The general goal of this study was to determine the diversity of TCRs from specific T cell populations, including T cells that are reactive with multiple ligands and TCRs that are reactive with a single peptide/MHC protein complex. (illinois.edu)
  • This high variability is mediated by cell clone-specific, adaptive receptors on B and T cells, called B cell receptors (BCRs) and T cell receptors (TCRs). (springermedizin.de)
  • Engagement of antigen-specific T cell receptors (TCRs) is a prerequisite for T cell activation. (axonmedchem.com)
  • Activation of T cells occurs upon ligation of clonotypic T cell receptors (TCRs) by MHC molecules on antigen-presenting cells (APCs) presenting peptides (peptide-MHC) from either endogenously encoded self molecules or exogenously encoded pathogen molecules. (axonmedchem.com)
  • By engineering T cells to express the TCRs researchers can endow any CD4+ cell with the capability to directly recognize tumor antigen-expressing cancer cells, without requiring presentation of the antigen by an antigen presenting cell. (roswellpark.org)
  • T cell receptor (TCR) gene transfer employing high affinity TCRs recognizing defined tumor-associated antigens can potentially circumvent these challenges. (washington.edu)
  • The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR. (wikipedia.org)
  • Thinking that they could try to train the transplanted immune cells to attack cancer cells, scientists transferred lymphocytes into a rat with carcinogen-induced sarcoma. (biolegend.com)
  • T cell receptors are protein complexes found on the surface of a type of white blood cell called T lymphocytes (or T cells), part of the body's immune system. (sciencephoto.com)
  • molecules on the surface of t-lymphocytes that recognise and combine with antigens . (biology-online.org)
  • In contrast, antigen receptors on B and T lymphocytes diversify enormously in each individual: genes for these receptors composed of multiple various parts are assembled randomly through gene recombination during development of these cells throughout the life of the individuals. (springer.com)
  • Recent reports on severe adverse events associated with treatment of cancer patients with CAR- or T-cell receptor (TCR)-engineered T lymphocytes further illustrate the critical importance of target selection for safe and efficient therapy ( 4-7 ). (aacrjournals.org)
  • The results show that a subpopulation of mature tumor-associated myeloid cells express high levels of arginase I, whereas tumor cells and infiltrating lymphocytes do not. (aacrjournals.org)
  • More recently, in vitro models suggest that stimulation of T cells in an l -Arginine ( l -Arg) poor microenvironment results in the induction of signal transduction and functional alterations (10) similar to those seen in tumor-infiltrating lymphocytes and peripheral blood T cells of patients with cancer. (aacrjournals.org)
  • The earliest application of T cells was in the allotransplant setting where donor lymphocytes were used for the treatment of relapsed leukaemias. (lymphomacoalition.org)
  • Signals propagated through the B cell antigen receptor (BCR) are vital for the development and survival of B lymphocytes in both the bone marrow and the periphery. (semanticscholar.org)
  • The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. (wikipedia.org)
  • These cells could directly recognize tumor cells by genetic modification to express a chimeric antigen receptor (CAR), and they were activated to exhibit a durable persistence in vivo through the T-cell activation endodomain with costimulatory signaling molecules [ 1 , 2 ]. (hindawi.com)
  • The TCR has to be efficiently expressed, their affinity to the desired antigen should be high enough to recognize low amounts of endogenously processed peptides on tumor cells, and the TCR should not be cross-reactive to other antigens. (mdc-berlin.de)
  • Although one TCR most efficiently bound MHC-multimers loaded with NY-ESO-1 peptide, T cells expressing this transgenic TCR were not able to recognize endogenously processed antigen. (mdc-berlin.de)
  • Merck, a leading science and technology company, today announced that it has evolved its agreement with Intrexon Corporation (NASDAQ: XON) for the development of Chimeric Antigen Receptor T-cell (CAR-T) therapies, genetically engineered T-cells with synthetic receptors that recognize a specific antigen expressed on tumor cells. (presseportal.ch)
  • CAR-T cells utilize designer fusion proteins to recognize and specifically destroy cells bearing a target surface epitope. (urotoday.com)
  • First-generation CARs depended heavily upon a single-chain fragment variable to recognize tumor-associated antigens specifically, however, they lacked the costimulatory intracellular molecule (e.g. (urotoday.com)
  • Receptors on innate immune cells that recognize pathogens, such as Toll-like receptors, have been diversified and selected through evolution. (springer.com)
  • Genetic engineering of immune cells called T cells, allows the T cells to recognize and kill tumor cells that have the specific protein on their cell surface. (ca.gov)
  • T cells charge into action when they recognize foreign substances, or antigens, on cells. (berkeleywellness.com)
  • T cells recognize foreign antigen through a heterodimeric $\alpha\beta$ T-cell receptor (TCR). (illinois.edu)
  • These T cells recognize foreign MHC proteins and because MHC proteins can each bind a variety of endogenous peptides, the T cells recognize multiple ligands (i.e., different peptide/MHC complexes). (illinois.edu)
  • The T cells are genetically modified to better recognize and attack cancer. (medworm.com)
  • CD4+ T cells recognize peptide fragments presented on MHC class II (HLA class II in humans). (roswellpark.org)
  • Autologous transplantation followed by treatment with CTL019 cells led to a complete response with no evidence of progression and no measurable serum or urine monoclonal protein at the most recent evaluation, 12 months after treatment. (nih.gov)
  • We characterized three NY-ESO-1 antigen-reactive cytotoxic T lymphocyte (CTL) clones which were generated by different approaches of T cell priming (autologous, allogeneic), and transferred their TCR into donor T cells for more extensive evaluations. (mdc-berlin.de)
  • CAR-T cells can be either derived from T cells in a patient's own blood (autologous) or derived from the T cells of another healthy donor (allogeneic). (wikipedia.org)
  • CAR-T cells may be manufactured either from the patient's own blood, known as an autologous treatment, or from the blood of a healthy donor, known as an allogeneic treatment. (wikipedia.org)
  • Not surprisingly, this first wave of trials will include many hematological malignancy trials, and that should include those with autologous cellular immunotherapies, such as CAR-T cells. (urotoday.com)
  • Generally, leukapheresis is utilized to collect peripheral blood mononuclear cells to create autologous therapy. (urotoday.com)
  • The purpose of this study is to test the safety of delivering the patients' own immune cells, called T cells, after the high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT). (clinicaltrials.gov)
  • JNJ-68284528 is an autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA). (centerwatch.com)
  • We investigated whether 2B4-enhanced activation signals can redirect the cytolytic function of human NK cells to NK cell-resistant and autologous leukemia and tumor targets. (aacrjournals.org)
  • Due to the high selectivity of the gene-modified NK cells for their tumor targets, NK cells from fully matched donors as well as autologous NK cells can be used. (aacrjournals.org)
  • Many malignant cells express MHC class I antigens and are thus naturally resistant to lysis by autologous NK cells. (aacrjournals.org)
  • Accordingly, the first clinical trials using adoptive transfer of autologous NK cells have failed to produce significant therapeutic effects ( 2 , 3 ). (aacrjournals.org)
  • Increasing awareness of the role of activating receptors in the recruitment of NK effector functions has motivated new efforts to target autologous malignancies. (aacrjournals.org)
  • Indeed, engagement of activating NK cell receptors by ligands expressed on tumor cells can overcome inhibitory signals and stimulate NK cell responses even in the presence of autologous MHC class I ( 6 , 7 ). (aacrjournals.org)
  • Although high dose chemotherapy, followed by autologous stem cell transplantation remains the standard of care at relapse, this treatment modality leads to a cure in less than 50% of the patients. (medworm.com)
  • High-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT) is the standard of care for relapsed or primary refractory (rel/ref) chemorefractory diffuse large B-cell lymphoma. (medworm.com)
  • The clinic offers integrated medical treatments like bio-cellular medicine treatments, adult autologous stem cell, general medical care, immunomodulating bio-enzyme systems, advanced ultrasonic diagnostic imaging, basic diagnostic tests, integrative medicine services, non-invasive regenerative procedures, nutrition counseling along with customized plans and wellness services to the patients. (placidway.com)
  • Accordingly, we developed a rhesus macaque (RM) model of neurotoxicity via adoptive transfer of autologous CD20-specific CAR T cells. (aacrjournals.org)
  • The peptide V beta 3-(57-77) also inhibited SEA-induced interferon-gamma production and SEA-induced proliferation of B10.BR spleen cells. (pnas.org)
  • The peptide inhibition of SEA-induced function was due at least in part to inhibition of V beta 3-bearing T-cell activity, since the percentage of T cells reactive with an anti-V beta 3 monoclonal antibody was significantly reduced by V beta 3-(57-77). (pnas.org)
  • A therapeutic T cell receptor mimic antibody targets tumor-associated PRAME peptide/HLA-I antigens. (sigmaaldrich.com)
  • Here, we have described Pr20, a TCR mimic (TCRm) human IgG1 antibody that recognizes the cell-surface ALY peptide/HLA-A2 complex. (sigmaaldrich.com)
  • The data provide rationale for developing TCRm antibodies as therapeutic agents for cancer, offer mechanistic insight on proteasomal regulation of tumor-associated peptide/HLA antigen complexes, and yield possible therapeutic solutions to target antigens with ultra-low surface presentation. (sigmaaldrich.com)
  • This complex participates in T-cell activation upon the presentation of the antigen peptide (derived from the foreign antigen) bound to the MHC (Class I and Class II) residing on antigen-presenting cells (APCs), including dendritic cells, macrophages and B cells. (wikipathways.org)
  • These findings are also discussed with regard to the potential for targeting autoimmune T cells and for peptide-based therapies that involve T-cell mediated tumor rejection. (illinois.edu)
  • Mice immunized with this peptide generate a diverse T cell response, recruiting T cells of multiple TCR Vbeta families and encompassing an avidity range of three logs. (washington.edu)
  • When the TCR engages with antigenic peptide and MHC (peptide/MHC), the T lymphocyte is activated through signal transduction, that is, a series of biochemical events mediated by associated enzymes, co-receptors, specialized adaptor molecules, and activated or released transcription factors. (wikipedia.org)
  • The Constant region is proximal to the cell membrane, followed by a transmembrane region and a short cytoplasmic tail, while the Variable region binds to the peptide/MHC complex. (wikipedia.org)
  • CDR3 is the main CDR responsible for recognizing processed antigen, although CDR1 of the alpha chain has also been shown to interact with the N-terminal part of the antigenic peptide, whereas CDR1 of the β-chain interacts with the C-terminal part of the peptide. (wikipedia.org)
  • Because cancer cells are produced by the body internally, they may not carry a foreign antigen on their surface, so T cells have trouble spotting them. (berkeleywellness.com)
  • Investigators optimized the design of CARs to enhance receptor mediated T cell signaling and demonstrated that second and third generation CARs, including various costimulatory molecules, resulted in enhanced T-cell persistence and sustained antitumor activity in both in vitro and in vivo mouse models as well as clinical trials. (nih.gov)
  • Therefore, target cell surface molecules can be found on the surface of NK cells. (plos.org)
  • This technique seems generalizable to biochemical and structural studies of many other cell surface molecules as well. (sciencemag.org)
  • Antigens (foreign proteins) are presented to T cell receptors by MHC molecules to effect an immune response. (sciencephoto.com)
  • left and middle) Individual BCR molecules in TIRF images from one typical μ-High or μ-Low J558L cell ( Video 1 ) indicating the instant diffusion coefficient (D 0 ) by pseudocolored spots. (rupress.org)
  • C-H) The D 0 values for all BCR molecules from μ-High and μ-Low J558L cells (C-E) or B1-8 primary B cells (F-H) labeled with Alexa Fluor 568-Fab anti-IgM placed on planar lipid bilayers containing no antigen, NIP1-His12, or pNP1-His12. (rupress.org)
  • 1 These costimulatory molecules successfully promote the production of cytokines such as IL-2 that activate, proliferate, and prolong survival of T cells. (urotoday.com)
  • While T-cell antigen receptor (TCR) recognizes antigenic peptides of proteins presented on the self MHC, B-cell antigen receptor (BCR) recognizes essentially any kinds of molecules. (springer.com)
  • Preclinical studies showed that inclusion of potent signaling molecules improves the antitumor activity of genetically modified T cells. (jcancer.org)
  • Subsequently, it was further documented that RP215 not only reacts with the epitope of immunoglobulin heavy chains, but also many other immunoglobulin superfamily (IgSF) proteins including antigen receptors, such as immunoglobulins and T-cell receptors, as well as cell adhesion molecules [ 3 , 4 ]. (omicsonline.org)
  • Tumor Necrosis Factor Receptor Superfamily Member 9 (4-1BB Ligand Receptor or T Cell Antigen 4-1BB Homolog or T Cell Antigen ILA or CD137 or TNFRSF9) pipeline Target constitutes close to 28 molecules. (researchandmarkets.com)
  • Several myeloma target antigens are being investigated in clinical trials of patients with R/R multiple myeloma, including B-cell maturation antigen (BCMA), CD38, CD138, SLAMF7, and natural killer group 2D. (medscape.com)
  • This article gives an overview on the state-of-the art of preclinical and clinical studies on suitable target antigens for CAR T cell therapy in AML patients. (mdpi.com)
  • Hematological malignancies tend to be more homogenous with a uniform expression of target antigens which may explain the high response rates and durability after CAR-T cell therapy. (urotoday.com)
  • Kimoto, Y. (1998) Expression of heavy-chain constant region of immunoglobulin and T-cell receptor gene transcripts in human non-hematopoietic tumor cell lines. (scirp.org)
  • Our data indicate that multiple parameters of TCR gene-modified T cells have to be evaluated to identify an optimal TCR candidate for adoptive therapy. (mdc-berlin.de)
  • Brummer T, Shaw PE, Reth M, Misawa Y (2002) Inducible gene deletion reveals different roles for B-Raf and Raf-1 in B-cell antigen receptor signalling. (springer.com)
  • Protein tyrosine phosphorylation subsequently leads to the activation of multiple pathways, including ERK (Extracellular Signal Regulated Kinase), JNK (c-Jun N-terminal Kinase), NF-κB (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and NFAT(Nuclear Factor of Activated T-Cells) pathways, which ultimately induce effector functions. (wikipathways.org)
  • ZAP70 also activates IKKs via the CARD11 (Caspase recruitment domain family, member 11) -BCL10 (B-Cell CLL/lymphoma-10)-MALT1 (Mucosa Associated Lymphoid Tissue Lymphoma Translocation Gene-1) complex and MAP3K (activated by PKCθ) which in turn relieve NF-κB of IκB (NF-kappa-B inhibitor beta) and allow its nuclear translocation and transcriptional activation. (wikipathways.org)
  • In addition, the safety of giving these gene modified cells to humans will be tested at different cell doses. (centerwatch.com)
  • Additional objectives are to determine if this therapy can cause regression of B cell cancers and to measure if the gene modified cells survive in patients blood. (centerwatch.com)
  • The success of adoptive T cell gene transfer for treatment of cancer and HIV is predicated on generating a response that is both durable and safe. (sciencemag.org)
  • These findings indicate that host immunosuppression before T cell transfer is not required to achieve long-term persistence of gene-modified T cells. (sciencemag.org)
  • Until recently, development of this technology has been limited by lack of efficient T cell culture systems and gene transfer techniques. (jcancer.org)
  • The MCL BCR seems to be antigen-experienced since it shows biased immunoglobulin heavy variable (IGHV) gene usage and suggestive patterns of clonal diversification despite low levels of somatic hypermutation. (haematologica.org)
  • Genetic profiling studies suggest that the normal counterpart of PCNSL cells are late germinal center (GC) exit B-cells with a gene expression profile characteristic of both GC B-cells and activated B-cells (ABC) ( 1 , 4 ). (frontiersin.org)
  • Then the lab [performs] a gene transfer, to teach the T cells to target a protein found on the surface of B cells , another type of blood cell that's affected in leukemia. (fightaging.org)
  • In this article, we describe a gene engineering strategy that efficiently modulates the balance of human NK cell signals toward tumor-specific activation. (aacrjournals.org)
  • Selecting highly tissue-restricted antigens, cancer testis antigens, mutated gene products or viral proteins as targets could significantly improve the safety profile of using CART cells. (aacrjournals.org)
  • To characterize these T cells at the molecular level, we compared the T cell antigen receptor (TcR) variable (V) region gene usage in thyroid, retroorbital, pretibial tissue, and peripheral blood mononuclear cells of two patients with Graves' disease, ophthalmopathy, and pretibial dermopathy. (uni-muenchen.de)
  • Since RP215 was shown to induce apoptosis and inhibit tumor growth in nude mouse models, the effects of RP215 and antibodies against antigen receptors on the gene regulations of cultured OC-3-VGH ovarian and C-33A cervical cancer cells were investigated through semi-quantitative RT-PCR. (omicsonline.org)
  • Among toll-like receptor genes (TLR-2, -3, -4, -6, -7 and -9), differential levels of gene expressions in different cancer cell lines were observed. (omicsonline.org)
  • Integration of B-cell receptor-induced ERK1/2 phosphorylation and mutations of SF3B1 gene refines prognosis in treatment-naïve chronic lymphocytic leukemia. (semanticscholar.org)
  • This invention describes sequences of TCR α and β chain genes from a novel tumor-recognizing CD4+ T cell clone as well as a method to prepare a large number of tumor recognizing CD4+ T cells by TCR gene transfer. (roswellpark.org)
  • Provision of "CD4 help" by current gene-engineered CD4+ T cells is expected to enhance the anti-tumor immune responses and overcome immunosuppression at the local tumor sites. (roswellpark.org)
  • Adoptive T-cell therapy of B-cell malignancies: conventional and physiological chimeric antigen receptors. (nih.gov)
  • We highlight advances in the use of CARs in the treatment of B-cell malignancies and future challenges in the use of adoptive therapy with CAR-engineered T cells. (nih.gov)
  • Recent studies have highlighted the successes of chimeric antigen receptor-modified T- (CART-) cell-based therapy for B-cell malignancies, and early phase clinical trials have been launched in recent years. (hindawi.com)
  • After two decades of preclinical research and clinical trials, the safety and feasibility of CART-cell-based therapy have been confirmed, and unprecedented clinical results have been obtained in hematological malignancies [ 3 - 5 ]. (hindawi.com)
  • These clinical studies indicate that CART-cell therapy can produce clinical responses in patients with advanced hematological malignancies. (hindawi.com)
  • Current status of clinical trials of chimeric antigen receptor-modified T (CART) cells in malignancies. (hindawi.com)
  • Maus MV, Grupp SA, Porter DL, June CH. Antibody-modified T cells: CARs take the front seat for hematologic malignancies. (springer.com)
  • In several human malignancies, the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is associated with aggressive characteristics and poor overall survival. (hindawi.com)
  • Porter DL, Kalos M, Zheng Z, Levine B, June C. Chimeric Antigen Receptor Therapy for B-cell Malignancies. (jcancer.org)
  • Expression is restricted to B cells, from the pro-B cell stage to mature B cells (though not on plasma cells), possibly follicular dendritic cells, and it is expressed on the surface of most B cell malignancies. (jcancer.org)
  • Given these preliminary findings, we have initiated a clinical trial to test the feasibility and safety of CART-19 cells in patients with CD19+ lymphoid malignancies. (jcancer.org)
  • This resulted in the development of targeted inhibitors for the treatment of several B-cell malignancies, especially chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). (haematologica.org)
  • Our data thus pave the way toward the clinical application of NK cells for the efficient and specific elimination of minimal residual tumor cells in various malignancies. (aacrjournals.org)
  • Several novel T cell-engaging therapies - including chimeric antigen receptor-modified T-cells (CART) and blinatumomab, a novel bispecific T-cell engaging (BiTE) single-chain antibody - have shown promise in the treatment refractory pediatric malignancies. (chop.edu)
  • However, patients with inherent- or acquiredresistance to first-line treatment options exhibit poor prognosis signifying the need for development of an optimal treatment approach for relapsed/ refractory malignancies of B cell origin. (pulsus.com)
  • Treating hematologic malignancies with chimeric antigen receptor T cells / James N. Kochenderfer. (nih.gov)
  • The vector encoded a chimeric antigen receptor (CAR) composed of CD4 linked to the CD3ζ signaling chain (CD4ζ). (sciencemag.org)
  • Antigen receptors, including immunoglobulins and T-cell receptors, are known to be widely expressed by cancer cells through unconfirmed mechanisms and for unknown purposes. (scirp.org)
  • RP215 is a monoclonal antibody generated against a carbohydrate-associated epitope of glycoproteins designated as CA215, which consists mainly of immunoglobulin superfamily proteins expressed by cancer cells including antigen receptors such as immunoglobulins and T-cell receptors. (omicsonline.org)
  • Chimeric antigen receptors (CARs) are synthetic proteins expressed on the surface of T cells. (medscape.com)
  • Here we have studied the dynamic activity of proteins involved in regulating actin polymerization in live T cells after activation. (nature.com)
  • Two such adaptor proteins, Nck and the Wiskott-Aldrich syndrome protein (WASp), were recruited to the TCR during initial T cell activation, where they colocalized with the tyrosine kinase Zap70. (nature.com)
  • Samelson, L.E. Signal transduction mediated by the T cell antigen receptor: the role of adaptor proteins. (nature.com)
  • Chimeric antigen receptors (CARs, also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors) are receptor proteins that have been engineered to give T cells the new ability to target a specific protein. (wikipedia.org)
  • This work prompted CD3ζ intracellular domains to be added to chimeric receptors with antibody-like extracellular domains, commonly single-chain fraction variable (scFV) domains, as well as proteins such as CD4, subsequently termed first generation CARs. (wikipedia.org)
  • Chimeric antigen receptors (CARs) are special receptors that are designed to bind to certain proteins on cancer cells. (ca.gov)
  • All the above components along with accessory proteins essential for MHC are a part of the immunological synapse that initiates T-cell activation. (wikipathways.org)
  • CD45 plays a role in antagonizing the effect of inhibitory proteins on T-cell activation. (wikipathways.org)
  • To generate T cells involved in transplant rejection, mice were injected at least two times (hyperimmunized) with cells that bear foreign MHC proteins and the "transplant-reactive" T cells were further enriched in culture. (illinois.edu)
  • 2004) Expression of immunoglobulin kappa light chain constant region in abnormal human cervical epithelial cells. (scirp.org)
  • Chen, Z. and Gu, J. (2007) Immunoglobulin G expression in carcinomas and cancer cell lines. (scirp.org)
  • 2007) Immunoglobulin alpha heavy chain derived from human epithelial cancer cells promotes the access of S phase and growth of cancer cells. (scirp.org)
  • 2007) Expression and secretion of immunoglobulin alpha heavy chain with diverse VDJ recombinations by human epithelial cancer cells. (scirp.org)
  • Statistical comparison of all inhibitory and activating killer cell immunoglobulin receptors (KIRs) between controls, survivors, and persons who died of Ebola virus disease in Guinea, 2015-2017. (cdc.gov)
  • Results from this study showed that: (1) unlike immunoglobulin genes, somatic mutations did not occur in TCR genes from "hyperimmune" animals and (2) TCR transcripts from "hyperimmune" T cells specific for foreign MHC were diverse in sequence. (illinois.edu)
  • In accordance with this, PCNSLs show rearranged immunoglobulin genes, ongoing somatic hypermutation, and persistent B cell lymphoma 6 (BCL6) activity but lack terminal B-cell differentiation resulting in a fixed IgM/IgD phenotype ( 5 - 8 ). (frontiersin.org)
  • Inhibitory receptors [e.g., killer immunoglobulin receptors (KIR)] interact with self-MHC class I antigens and protect normal cells from NK cell attack. (aacrjournals.org)
  • In this way the MHC-TCR-CD3 interaction for T cells is functionally similar to the antigen(Ag)-immunoglobulin(Ig)-FcR interaction for myeloid leukocytes, and Ag-Ig-CD79 interaction for B cells. (wikipedia.org)
  • The intracellular domains ensure intracellular signaling necessary to activate the effector functions of the CAR T cell. (medscape.com)
  • The successful use of chimeric antigen receptors (CARs) for the generation of antigen-specific effector T cells suggests that a similar approach could be used to generate alloantigen-specific Tregs. (jci.org)
  • Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma. (springer.com)
  • CARs are engineered receptors, stably or transiently transduced into T cells, that aim to enhance T cell effector function by recognizing and binding to a specific tumor-associated antigen. (mdpi.com)
  • Chimeric antigen receptors (CARs) significantly enhance the anti-tumor activity of immune effector cells. (ca.gov)
  • Safety evaluations will include a review of adverse events, laboratory test results, vital sign measurements, physical examination findings (including neurologic examination), assessment of cardiac function, immune effector cell-associated encephalopathy (ICE) score, handwriting assessment, and assessment of Eastern Cooperative Oncology Group (ECOG) performance status grade. (centerwatch.com)
  • More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-g, and TNF-α. (springer.com)
  • Acquisition of appropriate effector T cell function requires the participation of multiple signals from the T cell microenvironment. (axonmedchem.com)
  • Optimization of design, improving tumor microenvironment and combinations with other therapies may help us in improving CAR T cell efficacy. (springer.com)
  • In 2017, the Food and Drug Administration (FDA) approved tisagenlecleucel (Kymriah®) and axicabtagene ciloleucel (Yescarta®) CAR T-cell therapies for the treatment of certain relapsed or refractory leukemias and lymphomas. (cms.gov)
  • The first CAR-T cell therapies were FDA-approved in 2017, and there are now 5 approved CAR-T therapies. (wikipedia.org)
  • The reason this treatment option is appealing is that it is ready for immediate use, compared with other CAR therapies that require the use of a patient's own genetically modified T cells, which are then created through a multi-week manufacturing process, according to a press release issues by The University of Texas MD Anderson Cancer Center (MD Anderson). (curetoday.com)
  • Yet as a genitourinary oncologist, I have a mild sense of envy on this topic of CAR-T cell therapy, as I hope for a day where our patients can be treated with these exciting therapies. (urotoday.com)
  • Isolation and genetic modification of T cells for current CAR-T therapies are done on a patient-specific basis, which is time-consuming and expensive. (ca.gov)
  • As with all aggressive cancer therapies, CAR T-cell therapy has serious drawbacks. (berkeleywellness.com)
  • Autoimmune diseases such as lupus and rheumatoid arthritis lack therapies that specifically target only the disease-causing cells. (sciencemag.org)
  • A smooth translation from lab bench to clinical-grade GMP manufacturing is of particular importance for the development of successful CAR T cell therapies. (miltenyibiotec.com)
  • Therefore, arginase I production by mature myeloid cells in the tumor microenvironment may be a central mechanism for tumor evasion and may represent a target for new therapies. (aacrjournals.org)
  • Stem cell therapies have big potential and its usefulness for treating lung diseases can also have great appeal. (placidway.com)
  • Adoptive transfer of T cells engineered to express a chimeric antigen receptor (CAR) is an effective therapy for select lymphomas. (sciencemag.org)
  • When these cells were engineered to express a chimeric costimulatory receptor, they specifically recognized transformed, but not healthy, myeloid cell targets. (sciencemag.org)
  • We engineered human T cells to express a chimeric autoantibody receptor (CAAR), consisting of the PV autoantigen, desmoglein (Dsg) 3, fused to CD137-CD3ζ signaling domains. (sciencemag.org)
  • Together, our results demonstrate that use of CAR technology to generate potent, functional, and stable alloantigen-specific human Tregs markedly enhances their therapeutic potential in transplantation and sets the stage for using this approach for making antigen-specific Tregs for therapy of multiple diseases. (jci.org)
  • Targeting pathways that limit antigen-induced mast cell activation may have greater therapeutic efficacy by inhibiting the synthesis and release of many proinflammatory mediators produced in the mast cell. (aspetjournals.org)
  • The B-Cell Lymphoma Moon Shot is revolutionizing the conventional medical research approach to rapidly translate findings into patient treatment options and develop personalized therapeutic strategies. (mdanderson.org)
  • SLP-76 Coordinates Nck-dependent Wiskott-Aldrich syndrome protein recruitment with Vav-1/cdc42-dependent Wiskott-Aldrich syndrome protein activation at the T cell-APC contact Site. (nature.com)
  • 2001) Proteomic detection of changes in protein synthesis induced by NGX6 transfected in human nasopharyngeal carcinoma cells. (scirp.org)
  • ZAP70 induces activation of LAT (Linker for Activation of T-Cells), an integral membrane adaptor protein which further binds to GADS (Growth Factor Receptor-Bound Protein-2-Related Adaptor Protein-2), SLP76 (SH2 Domain-Containing Leukocyte Protein-76), and ITK (IL-2 inducible T-cell kinase). (wikipathways.org)
  • Engineered T cells are a promising form of synthetic biology for long-term delivery of protein-based therapeutics. (sciencemag.org)
  • The T cells are then transplanted back into the patient, where they hunt and kill anything with the protein attached to it. (fightaging.org)
  • Rituximab binds to CD20, a protein found on B cells, resulting in the killing of cancer cells. (lymphomacoalition.org)
  • In contrast, other part of the same antigen-specific CD4+ T cells, "non-tumor-recognizing CD4+ T cells (NTR-CD4)", only recognizes the exogenous tumor antigen protein after processing by antigen-presenting cells. (roswellpark.org)
  • these methods include protein production, X-ray crystallography, biophysics, and functional T-cell experiments. (jove.com)
  • Our results suggest that a cell surface protein(s) of 85 to 90 kDa is, or constitutes a portion of, a specific receptor for the PA. (asm.org)
  • CAR T cells are genetically engineered T cells with major histocompatibility complex-independent, tumor-specific, immune-mediated cytolytic actions against cancer cells. (springer.com)
  • T cells genetically engineered with chimeric antigen receptor (CAR) vectors can specifically target the surface antigen of cancer cells and kill them in an MHC-independent manner. (eurekaselect.com)
  • What is the efficacy of chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma? (medscape.com)
  • Celgene Corporation and bluebird bio has been granted Breakthrough Therapy Designation from FDA and Prime Eligibility from EMA for bb2121 Anti-BCMA CAR-T Cell Therapy for Relapsed and Refractory Multiple Myeloma. (marketresearch.com)
  • How these abundant receptors remain silent on resting B cells and how they can be activated by a molecularly diverse set of ligands is poorly understood. (nih.gov)
  • Similarly, T cells captured NKG2D and NKp46 ligands on tumor cells through trogocytosis and promoted NK cell activity [12] . (plos.org)
  • Current methods to generate alloantigen-specific Tregs rely on expansion with allogeneic antigen-presenting cells, which requires access to donor and recipient cells and multiple MHC mismatches. (jci.org)
  • Curing Ph+ ALL: assessing the relative contributions of chemotherapy, TKIs, and allogeneic stem cell transplant. (medworm.com)
  • Hitherto, allogeneic hemotopoietic stem cell transplantation (allo-HSCT) is the best curative treatment option in intermediate and high risk AML. (mdpi.com)
  • This is the basis for the graft-versus-leukemia (GVL) effect, which contributes in part to the efficacy of allogeneic stem cell transplantation (SCT) and is the rationale for donor lymphocyte infusion in leukemia. (bloodjournal.org)
  • We are encouraged by the results of the clinical trial, which will launch further clinical studies to investigate allogeneic cord blood-derived CAR NK cells as a potential treatment option for patients in need," corresponding author Dr. Katy Rezvani, professor of stem cell transplantation and cellular therapy at MD Anderson, said in a press release. (curetoday.com)
  • 50%, despite allogeneic stem cell transplant following second remission. (centerwatch.com)
  • This strategy promises to extend the use of NK cells in cancer therapy beyond allogeneic mismatched hematopoietic stem cell transplantation. (aacrjournals.org)
  • Structures of many of the cell surface receptor-ligand complexes mediating the interactions between T cells and target cells have been determined in the past ten years. (nih.gov)
  • Chang CC, Campoli M, Ferrone S. Classical and nonclassical HLA class I antigen and NK Cell-activating ligand changes in malignant cells: current challenges and future directions. (springer.com)
  • The CAR consists of an antibody or ligand-derived targeting ectodomain fused with a hinge, a trans-membrane domain, and intracellular T cell signaling domains. (frontiersin.org)
  • The interaction of the T cell receptor for antigen (TCR) with its antigen-major histocompatibility complex ligand is difficult to study because both are cell surface multimers. (sciencemag.org)
  • AICD in T cells has been suggested to be mediated mainly by Fas (CD95)/Fas-ligand (Fas-L) interaction ( 6 ), and also has been modulated by environmental constituents ( 7 , 8 ). (jimmunol.org)
  • The T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the α and β chains, and a signaling subunit, namely the CD3ε, γ and δ chains and the TCRζ chain. (wikipathways.org)
  • Interestingly, these signals are known to be either ligand-independent ('tonic' signals) or induced by ligand (antigen) binding to the BCR. (semanticscholar.org)
  • Additionally, an incidental match between male HLA-C2 and female HLA-C1 ligand KIR receptors might perturb the balance between activatory and inhibitory KIR-ligand interactions during pregnancy in couples affected by RPL. (physiciansweekly.com)
  • Tumor Necrosis Factor Receptor Superfamily Member 9 (4-1BB Ligand Receptor or T Cell Antigen 4-1BB Homolog or T Cell Antigen ILA or CD137 or TNFRSF9) - Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD137 is a member of the tumor necrosis factor (TNF) receptor family. (researchandmarkets.com)
  • The latest report Tumor Necrosis Factor Receptor Superfamily Member 9 - Pipeline Review, H1 2018, outlays comprehensive information on the Tumor Necrosis Factor Receptor Superfamily Member 9 (4-1BB Ligand Receptor or T Cell Antigen 4-1BB Homolog or T Cell Antigen ILA or CD137 or TNFRSF9) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (researchandmarkets.com)
  • It also reviews key players involved in Tumor Necrosis Factor Receptor Superfamily Member 9 (4-1BB Ligand Receptor or T Cell Antigen 4-1BB Homolog or T Cell Antigen ILA or CD137 or TNFRSF9) targeted therapeutics development with respective active and dormant or discontinued projects. (researchandmarkets.com)
  • We'll be discussing immune checkpoint blockade (and one of our new product lines, GoInVivo ™) in another blog, however this post will focus on another type of immune therapy, called adoptive cell transfer, also known as ACT. (biolegend.com)
  • We have examined the interaction of the microbial superantigen staphylococcal enterotoxin A (SEA) with peptides corresponding to overlapping regions of the T-cell antigen receptor beta chain variable region V beta 3. (pnas.org)
  • These data indicate that the 2B4 receptor has a potent costimulatory effect in NK cells. (aacrjournals.org)
  • Initial studies of CAR T cell therapy have shown promising results in ovarian cancer, but there are some obstacles like impaired T cell trafficking, lack of antigenic targets, cytokine release syndrome and most important immunosuppressive tumor microenvironment. (springer.com)
  • The majority of patients who received CAR T-cell therapy also experienced adverse events including cytokine release syndrome and neurologic effects. (cms.gov)
  • Supraphysiologic T-cell proliferation, a hallmark of this therapy, contributes to both efficacy and the most notable toxicity, cytokine release syndrome (CRS), posing a unique challenge for toxicity management. (bloodjournal.org)
  • Mast cell activation results in the immediate release of proinflammatory mediators prestored in cytoplasmic granules, as well as initiation of lipid mediator production and cytokine synthesis by these resident tissue leukocytes. (aspetjournals.org)
  • Here, using a panel of mice lacking various combinations of adenosine receptors, and mast cells derived from these animals, we show that adenosine receptor agonists provide an effective means of inhibition of mast cell degranulation and induction of cytokine production both in vitro and in vivo. (aspetjournals.org)
  • We identify A 2B as the primary receptor limiting mast cell degranulation, whereas the combined activity of A 2A and A 2B is required for the inhibition of cytokine synthesis. (aspetjournals.org)
  • Chen D, Heath V, O'Garra A, Johnston J, McMahon M (1999) Sustained activation of the raf-MEK-ERK pathway elicits cytokine unresponsiveness in T cells. (springer.com)
  • Grade 3+ cytokine release syndrome was associated with polyfunctional T cells, and both grade 3+ neurologic toxicity (NT) and antitumor efficacy were associated with polyfunctional IL-17A-producing T cells. (bloodjournal.org)
  • The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro . (springer.com)
  • Chimeric 2B4 signaling alone failed to induce interleukin-2 receptor up-regulation and cytokine secretion but triggered a specific degranulation response. (aacrjournals.org)
  • Clinical studies conducted by physician scientists at the CCCR have demonstrated that administration of tocilizumab - a recombinant humanized anti-IL6 receptor monoclonal antibody that interferes with secretion of the cytokine IL6 - can be an effective treatment for pediatric patients who develop CRS after CART or BiTE therapy. (chop.edu)
  • The first chimeric receptors containing portions of an antibody and the T cell receptor was described in 1987 by Yoshikazu Kuwana et al. (wikipedia.org)
  • In 1991, chimeric receptors containing the intracellular signaling domain of CD3ζ were shown to activate T cell signaling by Arthur Weiss at the University of California, San Francisco. (wikipedia.org)
  • They engineered T cells to express chimeric receptors consisting of the disease-causing autoantigen desmoglein 3 fused to signaling domains that activate T cells. (sciencemag.org)
  • This approach has been tested in vitro with CD30+ hematopoietic stem cells and CD30+ tumor cells and in vivo in mice transplanted with human CD30+ hematopoietic stem cells. (innovations-report.com)
  • In vivo experiments provided evidence that the treatment with anti-CD30 T-cells has no unwanted impact on the endogenous immune system. (innovations-report.com)
  • Additionally, CAR-NK cells demonstrate in vivo activity similar to that of CAR-T cells, but with less toxicity. (ca.gov)
  • Dsg3 CAAR-T cells exhibit specific cytotoxicity against cells expressing anti-Dsg3 BCRs in vitro and expand, persist, and specifically eliminate Dsg3-specific B cells in vivo. (sciencemag.org)
  • We presented data showing that the CART-19 cells expressing the 4-1BB signaling domain can have unprecedented and massive in-vivo expansion, traffic to tumor sites, persist long term in vivo, and induce rapid and potent anti-tumor activity in chemotherapy refractory CLL patients. (jcancer.org)
  • Therefore, most clinical applications have resulted in limited in vivo expansion and persistence of CAR-modified T cells resulting in disappointing clinical activity 3 , 4 . (jcancer.org)
  • By inclusion of the 4-1BB signaling domain, in vitro tumor cell killing, and in-vivo anti-tumor activity and persistence of CART-19 cells in a murine xenograft model of human ALL is greatly enhanced 7 . (jcancer.org)
  • 6 , 7 In addition, the BCR pathway is active in MCL cells in vitro and in vivo , and inhibiting the partially overexpressed key molecule Syk resulted in the induction of apoptosis in vitro . (haematologica.org)
  • The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. (springer.com)
  • EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro . (springer.com)
  • Differential regulation of T-cell dependent and T-cell independent antibody responses through arginine methyltransferase PRMT1 in vivo. (semanticscholar.org)
  • We have discussed basic functioning of CAR T cells, their rationale and clinical outcome in ovarian cancer with limitations. (springer.com)
  • A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16(ecto) directed chimeric antigen receptors for recurrent ovarian cancer. (springer.com)
  • Recent published clinical studies on CART cells specific for solid tumor antigens. (hindawi.com)
  • While success has been achieved in a number of studies, and two CAR-T-cell products were recently approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) (YESCARTA ® , KYMRIAH ® ), this treatment modality continues to present challenges for clinical development. (springer.com)
  • We anticipate these modifications will further expand CAR T cell therapy in clinical practice. (frontiersin.org)
  • Thus, the CAR is most suitable for clinical application in targeting CD30+ leukemia and lymphoma cells. (innovations-report.com)
  • A clinical study phase I is planned for early 2016, indication: cutaneous T-cell lymphoma. (innovations-report.com)
  • While most clinical approaches have focused on CD8+ T cells, the importance of CD4+ T cells in mediating tumor regression has become apparent. (jci.org)
  • In this review, we provide a summary of CAR T cell preclinical studies and clinical trials for malignant pleural mesothelioma (MPM), a rare, locally invasive pleural cancer with poor prognosis. (mdpi.com)
  • A first generation CAR containing a CD4 extracellular domain and a CD3ζ intracellular domain was used in the first clinical trail of chimeric antigen receptor T cells by the biotechnology company Cell Genesys in the mid 1990s, allowing adoptively transferred T cells to target HIV infected cells, although it failed to show any clinical improvement. (wikipedia.org)
  • The polyfunctionality strength index of manufactured CAR T cells were associated with clinical response and toxicities. (bloodjournal.org)
  • However, the association of preinfusion CAR product T-cell functionality with clinical outcomes has not been reported. (bloodjournal.org)
  • A prespecified T-cell polyfunctionality strength index (PSI) applied to preinfusion CAR product was significantly associated with clinical response, and PSI combined with CAR T cell-expansion or pretreatment serum IL-15 levels conferred additional significance. (bloodjournal.org)
  • Within the total product cell population, associations with clinical outcomes were greater with polyfunctional CD4+ T cells compared with CD8+ cells. (bloodjournal.org)
  • The findings in this exploratory study show that a preinfusion CAR product T-cell subset with a definable polyfunctional profile has a major association with clinical outcomes of CAR T-cell therapy. (bloodjournal.org)
  • In clinical trials, CAR T-cell therapy has emerged as an approach that can elicit long-lasting remission in hard-to-treat blood cancers. (berkeleywellness.com)
  • During early clinical trials, most patients developed an immune reaction to the infusion of CAR T cells. (berkeleywellness.com)
  • We report long-term results from three clinical trials to evaluate gammaretroviral vector-engineered T cells for HIV. (sciencemag.org)
  • Except for a few indolent cases, MCL typically has a rapid growth requiring immediate treatment, which places MCL in clinical proximity to other aggressive lymphomas such as diffuse large B cell lymphoma (DLBCL). (springermedizin.de)
  • Miltenyi Biotec offers product solutions for both CAR T cell research and clinical manufacturing needs. (miltenyibiotec.com)
  • A number of clinical trials have examined the use of CAR T-cell therapy. (lymphomacoalition.org)
  • To do this, they transfected a patient's own T cells with special T cell receptors that are engineered to be specific to a tumor antigen. (biolegend.com)
  • Doctors must use an individual patient's T cells so the immune system doesn't reject them. (berkeleywellness.com)
  • For this method, the researchers harvest a patient's T cells using a process like blood transfusion. (fightaging.org)
  • Chimeric antigen receptor T-cell, or CAR T-cell, therapy involves the laboratory reprogramming of a patient's T cells, which are a type of white blood cell responsible for protecting the body against infection and disease. (medworm.com)
  • City of Hope will re-engineer a patient's immune system central memory T cells (TCM cells) to express chimeric antigen receptors (CAR). (ca.gov)
  • Stem cell therapy for autism can enhance the blood and oxygen flow to the patient's brain by stimulating the formation of new arteries and by replacing the damaged neurons. (placidway.com)
  • White blood cells that include T cells are removed from the patient's body through a process called leukapheresis . (lymphomacoalition.org)
  • To our knowledge, this is the first report that describes the increased cytotoxicity of NK cells following the acquisition of CARs via trogocytosis. (plos.org)
  • RP215 and anti-antigen receptor antibodies were equally effective in inducing apoptosis and complement-dependent cytotoxicity reactions to cultured cancer cells. (scirp.org)
  • CAR-T cells destroy cells through several mechanisms, including extensive stimulated cell proliferation, increasing the degree to which they are toxic to other living cells (cytotoxicity) and by causing the increased secretion of factors that can affect other cells such as cytokines, interleukins and growth factors. (wikipedia.org)
  • An afucosylated Fc form (Pr20M) directed antibody-dependent cellular cytotoxicity against PRAME+HLA-A2+ leukemia cells and was therapeutically effective against mouse xenograft models of human leukemia. (sigmaaldrich.com)
  • In addition, it induced dose-dependent relative cytotoxicity against these lymphoma cells when incubated with PBMCs. (frontiersin.org)
  • For example, though chemotherapy could kill cancer cells through a cytotoxic treatment, it would also kill healthy cells and lead to a number of undesirable side effects. (biolegend.com)
  • The cancer-testis antigen NY-ESO-1 has been used as a target for different immunotherapies like vaccinations and adoptive transfer of antigen-specific cytotoxic T cells, as it is expressed in various tumor types and has limited expression in normal cells. (mdc-berlin.de)
  • When they come in contact with their targeted antigen on a cell, CAR-T cells bind to it and become activated, then proceed to proliferate and become cytotoxic. (wikipedia.org)
  • Prior to CAR-T cell infusion, cytotoxic chemotherapy may include cyclophosphamide and/or fludarabine. (urotoday.com)
  • When conjugated to Pseudomonas Exotoxin A (ETA´), the PCNSL reactive epitope exerts cytotoxic effects on lymphoma cells expressing a SAMD14/neurabin-I reactive BCR. (frontiersin.org)
  • Blinatumomab is superior to standard chemotherapy for children and young adults with high- or intermediate-risk B-cell acute lymphoblastic leukemia that has relapsed. (medworm.com)
  • Side effects experienced by participants were primarily related to the conditioning chemotherapy given before cell infusion and were resolved within one to two weeks, Rezvani said in the release. (curetoday.com)
  • 2 Fourth generation CARs, termed TRUCKS, add a proinflammatory factor such as IL-12 to provide higher tumor cell kill and potentially avoid the need for preparatory or conditioning chemotherapy. (urotoday.com)
  • Patients between greater than or equal to 3 years and less than or equal to 30 years of age, with CD19+/CD22+ B cell ALL or lymphoma who have relapsed or have refractory disease after at least one standard chemotherapy regimen and one salvage regimen, with no alternative curative options who meet standard Phase I eligibility criteria. (centerwatch.com)
  • Before the CAR T cells are infused into the bloodstream, the patient might need to undergo chemotherapy a few days before to reduce the number of other immune cells. (berkeleywellness.com)
  • Response rates for patients with B-cell neoplasms such as Non-Hodgkin's Lymphoma (NHL) and Acute Lymphoblastic Leukemia (ALL) treated with traditional modalities, including chemotherapy, radiation, and bone marrow transplant, are relatively high. (pulsus.com)
  • Prior to the patient being infused with the harvested CAR T cells, they may receive lymphodepleting chemotherapy to reduce the level of white blood cells and help the body accept the reprogrammed T cells. (lymphomacoalition.org)
  • May participate in suppression of cell proliferation and induces apoptotic cell death through activation of interleukin-1-beta converting enzyme (ICE)-like proteases. (uniprot.org)
  • Monitoring CAR T-cell polyfunctionality as a key product attribute may complement other characteristics including T-cell proliferation. (bloodjournal.org)
  • This may permit homeostatic proliferation of the infused T cells, eliminate competitive T cells that could serve as a "sink" for important activating cytokines, result in elimination of regulatory and suppressive T cells or even enhance endogenous host APC activity 8 . (jcancer.org)
  • This is a diagnostic hallmark of the disease and of high pathobiological relevance as cyclin D1 plays a major role in cell cycle control and therefore in proliferation (see below). (springermedizin.de)
  • l -Arg depletion by tumor-associated myeloid cells blocked the re-expression of CD3ζ in stimulated T cells and inhibited antigen-specific proliferation of OT-1 and OT-2 cells. (aacrjournals.org)
  • miR-18a Inhibitor Suppresses Leukemia Cell Proliferation by Upregulation of PTEN Expression. (physiciansweekly.com)
  • During this time, scientists were mainly limited to cells that could be taken from one animal and directly placed into another animal, but this changed over the next few decades, particularly after the discovery of IL-2 and its ability to help expand T cells in vitro prior to (and during) its injection into the host, amplifying the anti-tumor response from transfer. (biolegend.com)
  • In vitro studies using cultured human and mouse mast cells, and studies of mice lacking A 2B receptors, suggest that adenosine receptors, specifically the G s -coupled A 2A and A 2B receptors, might provide such a target. (aspetjournals.org)
  • Results showed that: (1) T cells that are specific for the p2Ca/L$\sp{\rm d}$ complex can be readily generated in vitro and (2) the T cells express a diverse TCR repertoire, although restrictions in the use of V$\beta$ and J$\beta$ regions were observed. (illinois.edu)
  • Tumor-associated myeloid cells also expressed high levels of cationic amino acid transporter 2B, which allowed them to rapidly incorporate l -Arginine ( l -Arg) and deplete extracellular l -Arg in vitro . (aacrjournals.org)
  • Lee, G. and Liu, S. (2013) Roles of antigen receptors and CA215 in the innate immunity of cancer cells. (scirp.org)
  • Taken together, we propose that hypoxia is a critical determinant of survival of the activated T cells via the HIF-1α-AM cascade, defining a previously unknown mode of regulation of peripheral immunity. (jimmunol.org)
  • Subsequently, accumulated T cells may need to be cleared away to prevent a harmful over-response or for preservation of homeostasis within the T cell compartment of peripheral immunity. (jimmunol.org)
  • Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. (sciencemag.org)
  • The innate immunity of cancer cells can also be affected by any of these antibodies through unidirectional regulations of certain toll-like receptors. (omicsonline.org)
  • Therefore, the anti-cancer therapy of RP215 Mab may be, in part related to the surface bound antigen receptors and/or toll-like receptors in the innate immunity system, all of which may be involved in the growth and survival of cancer cells. (omicsonline.org)
  • Another approach in the development of immunotherapies is the use of cellular immunity with T cells. (lymphomacoalition.org)
  • Cellular immunity, also called cell-mediated immunity, is the response of the body's immune system to harmful invading foreign organisms. (lymphomacoalition.org)
  • These receptors have both extracellular and intracellular components. (medscape.com)
  • The CAR itself is a chimeric recombinant molecule that encompasses an extracellular antigen identification zone for Signal 1, a spacer, a transmembrane zone, and intracellular signaling moieties that facilitate Signal 2 costimulation and resultant signal transduction. (urotoday.com)
  • These data suggest that the region of V beta 3 encompassing amino acids 57-77 is an area that displays the appropriate sequence and conformation for binding of the SEA molecule and blocking of the resultant interaction with the T-cell antigen receptor. (pnas.org)
  • The CAR "generation" typically refers to the intracellular signaling domains incorporated in the receptor molecule. (frontiersin.org)
  • Molecular model of the alphabeta T cell receptor bound to the influenza haemagglutinin antigen and MHC class II molecule HLA-DR1. (sciencephoto.com)
  • A and B) The μ-High and μ-Low J558L cells labeled with Alexa Fluor 568-Fab anti-IgM were placed on planar lipid bilayers lacking antigen (A) or containing NIP1-His12 (B), and single BCR molecule TIRF images were acquired. (rupress.org)
  • They do this by adding an artificial chimeric antigen receptor, which locks on to a matching molecule on cancer cells. (berkeleywellness.com)
  • First-generation CARs typically utilized the intracellular domain of the CD3z chain only, the primary signaling molecule from endogenous T-cell receptors. (jcancer.org)
  • The signaling lymphocyte activation molecule-related receptor 2B4 (CD244) is an important regulator of NK cell activation. (aacrjournals.org)
  • Campoli M, Ferrone S. HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. (springer.com)
  • Potentially malignant cells are continuously eliminated by apoptosis and the immune system, but cancers have escaped these mechanisms. (bloodjournal.org)
  • These trials ultimately led to the first FDA approvals of CAR T cells in 2017 for tisagenlecleucel (Kymriah), marketed by Novartis originally for B-cell acute lymphoblastic leukemia (B-ALL), and axicabtagene ciloleucel (Yescarta), marketed by Kite Pharma originally for Diffuse Large B-cell lymphoma (DLBCL). (wikipedia.org)
  • In this study, the researchers administered a single dose of the CAR NK-cell therapy at one of three dose levels to 11 patients - five of whom had chronic lymphocytic leukemia (CLL) and six who were diagnosed with non-Hodgkin lymphoma. (curetoday.com)
  • Early studies with CAR-T cell therapy showed impressive efficacy in chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and refractory B cell lymphoma. (urotoday.com)
  • After treatment with chimeric antigen receptor (CAR) T cells, interleukin (IL)-15 elevation and CAR T-cell expansion are associated with non-Hodgkin lymphoma (NHL) outcomes. (bloodjournal.org)
  • In the study , led by the National Cancer Institute, 101 adult patients with an aggressive form of B-cell lymphoma underwent CAR T-cell therapy. (berkeleywellness.com)
  • To target this antigen, CAR T cells have gained great success in treating patients with B cell leukemia and lymphoma. (eurekaselect.com)
  • The past two decades of lymphoma research have uncovered the essential role of the B-cell antigen receptor (BCR) pathway in lymphoma biology. (haematologica.org)
  • This post-translational modification of neurabin-I and SAMD14 seems to lead to a chronic immune reaction with B-cell receptor activation contributing to lymphoma genesis of PCNSLs. (frontiersin.org)
  • Specific binding of the prokaryotically produced SAMD14/neurabin-I Fab-antibody to lymphoma cells and their internalization were determined by flow cytometry. (frontiersin.org)
  • The IgG1-format SAMD14/neurabin-I construct was found to specifically bind to target lymphoma cells expressing a SAMD14/neurabin-I reactive B cell receptor. (frontiersin.org)
  • Over time, FL could acquire additional genetic mutations and transform into diffuse large B-cell lymphoma, a more aggressive B-cell neoplasm, which markedly reduces survival. (medworm.com)
  • At the University of Pennsylvania alone, Dr. Schuster said more than 200 patients had been treated with CAR T-cell therapy when factoring in the patients with acute lymphocytic leukaemia as well as those with lymphoma. (lymphomacoalition.org)
  • CAR T Cells: Engineering Patients' Immune Cells to Treat Their Cancers. (medscape.com)
  • Smith AJ, Oertle J, Warren D, Prato D. Chimeric antigen receptor (CAR) T cell therapy for malignant cancers: summary and perspective. (springer.com)
  • Targeted drugs, such as monoclonal antibodies directed at specific tumor antigens, made a big impact on how cancers were treated in that they could attack transformed cells while leaving the healthy cells alone. (biolegend.com)
  • However, these were still limited in that the treatments were very specific to a particular tumor cell type, and thus could only treat certain cancers (and sometimes, only very rare cancers). (biolegend.com)
  • The first major driving force to treating cancers through ACT was the discovery in the mid 1960s that immune cells were responsible for tissue transplant rejection, or graft-versus-host disease (GVHD). (biolegend.com)
  • CMS initiates this national coverage analysis for Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers. (cms.gov)
  • Preferentially expressed antigen in melanoma (PRAME) is a cancer-testis antigen that is expressed in many cancers and leukemias. (sigmaaldrich.com)
  • B-cell leukemias and lymphomas are cancers that are often difficult to treat. (centerwatch.com)
  • those included three people whose cancers spread beyond the blood cells the new treatment targets. (fightaging.org)
  • Technology potentially provides compositions and methods for prophylaxis and/or therapy for a variety of cancers which express a NY-ESO-1 antigen. (roswellpark.org)
  • Human papilloma virus (HPV)-targeted T cell therapy for patients with HPV-associated cancers / Christian S. Hinrichs. (nih.gov)
  • Roswell researchers have discovered that there are two distinct types of tumor antigen-specific CD4+ T cells. (roswellpark.org)
  • A part of tumor antigen-specific CD4+ T cells, that we named "tumor-recognizing CD4+ T cells (TR-CD4)", directly recognizes MHC class II-expressing cancer cells in antigen-specific and MHC class II-restricted manners. (roswellpark.org)
  • Jordan, M.S., Singer, A.L. & Koretzky, G.A. Adaptors as central mediators of signal transduction in immune cells. (nature.com)
  • Lim WA, June CH. The principles of engineering immune cells to treat cancer. (springer.com)
  • In the 1980s, Dr. Zelig Eshhar and his lab thought of the idea of altering immune cells prior to adoptive transfer so that they could more specifically target tumor cells. (biolegend.com)
  • Transferring large amounts of overactive immune cells does have some negative consequences. (biolegend.com)
  • Trogocytosis is a process in which membrane patches are exchanged between target and immune cells [5] - [7] . (plos.org)
  • Because the therapy consists of living immune cells, it represents something truly revolutionary: a living drug. (berkeleywellness.com)
  • A trial has been running in leukemia patients using immune cells modified to express a variety of chimeric antigen receptors . (fightaging.org)
  • Recently, chimeric antigen receptor-modified T- (CART-) cell-based therapy, an innovative approach to tumor treatment, was demonstrated to potentially exhibit MHC-independent antitumor effects. (hindawi.com)
  • Affinity-tuned cells exhibited robust antitumor efficacy similar to high-affinity cells, but spared normal cells expressing physiologic target levels. (aacrjournals.org)
  • 3. Studies on the average avidity of the antibody produced by specific plaque-forming cells. (nature.com)
  • Liu, Y. J., Oldfield, S. & MacLennan, I. C. Memory B cells in T cell-dependent antibody responses colonize the splenic marginal zones. (nature.com)
  • CARs have a single-chain variable fragment (scFv), which is derived from the part of an antibody that is specific to an antigen. (biolegend.com)
  • Recently, a monoclonal antibody, designated as RP215, was generated against the ovarian cancer cell line, OC-3-VGH, and was shown to react with CA215, which consisted mainly of these cancer cell-expressed antigen receptors. (scirp.org)
  • Anti-θAKR antibody conjugated to fluorescein has been used in direct immunofluorescence tests to identify spleen θ + (T) sheep erythrocyte rosette-forming cells in AKR mice. (rupress.org)
  • When given to diseased mice, the engineered T cells targeted and killed B cells that express antibodies targeting desmoglein 3, hinting that such a strategy may be an effective way to treat antibody-driven autoimmune diseases. (sciencemag.org)
  • CAAR-T cells may provide an effective and universal strategy for specific targeting of autoreactive B cells in antibody-mediated autoimmune disease. (sciencemag.org)
  • The SAMD14/neurabin-I Fab antibody bound specifically to DLBCL cells expressing a BCR with reactivity to SAMD14/neurabin-I and not to unmanipulated DLBCL cell lines. (frontiersin.org)
  • RP215 is a monoclonal antibody (Mab) generated against an ovarian cancer cell line, OC-3-VGH in 1987 and shown to react with the carbohydrate-associated epitope of glycoproteins known as CA215 expressed by cancer cells [ 1 , 2 ]. (omicsonline.org)
  • Whereas the antibody uses its Fc region to bind to Fc Receptors on leukocytes, TCR is already docked onto the cell membrane. (wikipedia.org)
  • For safety, CAR-T cells are engineered to be specific to an antigen expressed on a tumor that is not expressed on healthy cells. (wikipedia.org)
  • Furthermore, selected toll-like receptor genes (TLR- 2, -3, -4, and -9) were also found to be highly regulated by both RP215 and anti-antigen receptor antibodies. (scirp.org)
  • For example, RP215 and anti-antigen receptor antibodies were found to both up-regulate TLR-2 and/or TLR-3 and down- regulate TLR-4 and TLR-9 intwo types of cancer cells. (scirp.org)
  • For both cell lines, RP215 and anti-antigen receptors were found to regulate similarly and consistently a number of genes including NFκB-1, IgG, P21, Cyclin D1, ribosomal P1 and c-fos with only exceptions for EGFR and ribosomal P0. (omicsonline.org)
  • Based on these preliminary observations, it can be proposed that apoptosis of the two cancer cell lines was induced similarly by RP215 and anti-antigen receptors through consistent regulations of the same groups of genes. (omicsonline.org)
  • In addition to antigen-presenting cells such as macrophages and dendritic cells, many human cancer cells express MHC class II constitutively or in an IFN-γ-inducible manner although the role of MHC class II expression on human cancer cells is largely unknown. (roswellpark.org)