Antigens: Substances that are recognized by the immune system and induce an immune reaction.Antigens, CD: 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.Antigens, CD8: 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.Antigens, Neoplasm: 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, CD3: 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).Antigens, Surface: 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.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Antigens, CD38: 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.Antigens, CD34: Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.Antigens, CD19: Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.Antigens, CD40: 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.CD40 Ligand: 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.Antigens, CD20: Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Antigens, CD28: Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.Antigens, CD44: Acidic sulfated integral membrane glycoproteins expressed in several alternatively spliced and variable glycosylated forms on a wide variety of cell types including mature T-cells, B-cells, medullary thymocytes, granulocytes, macrophages, erythrocytes, and fibroblasts. CD44 antigens are the principle cell surface receptors for hyaluronate and this interaction mediates binding of lymphocytes to high endothelial venules. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)Antigens, CD7: Differentiation antigens expressed on pluripotential hematopoietic cells, most human thymocytes, and a major subset of peripheral blood T-lymphocytes. They have been implicated in integrin-mediated cellular adhesion and as signalling receptors on T-cells.Antigens, CD14: Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.Antigens, CD2: Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.CD4-CD8 Ratio: Ratio of T-LYMPHOCYTES that express the CD4 ANTIGEN to those that express the CD8 ANTIGEN. This value is commonly assessed in the diagnosis and staging of diseases affecting the IMMUNE SYSTEM including HIV INFECTIONS.Antigens, CD5: 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)Antigens, Differentiation: 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.CD4-Positive T-Lymphocytes: 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.Antigens, CD1: 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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antigens, CD56: The 140 kDa isoform of NCAM (neural cell adhesion molecule) containing a transmembrane domain and short cytoplasmic tail. It is expressed by all lymphocytes mediating non-MHC restricted cytotoxicity and is present on some neural tissues and tumors.Antigens, Differentiation, T-Lymphocyte: Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.ADP-ribosyl Cyclase: A membrane-bound or cytosolic enzyme that catalyzes the synthesis of CYCLIC ADP-RIBOSE (cADPR) from nicotinamide adenine dinucleotide (NAD). This enzyme generally catalyzes the hydrolysis of cADPR to ADP-RIBOSE, as well, and sometimes the synthesis of cyclic ADP-ribose 2' phosphate (2'-P-cADPR) from NADP.Antigens, Differentiation, Myelomonocytic: Surface antigens expressed on myeloid cells of the granulocyte-monocyte-histiocyte series during differentiation. Analysis of their reactivity in normal and malignant myelomonocytic cells is useful in identifying and classifying human leukemias and lymphomas.Antigens, CD80: 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.Antigens, CD53: Tetraspanin proteins found at high levels in cells of the lymphoid-myeloid lineage. CD53 antigens may be involved regulating the differentiation of T-LYMPHOCYTES and the activation of B-LYMPHOCYTES.Antigens, CD24: A cell adhesion protein that was originally identified as a heat stable antigen in mice. It is involved in METASTASIS and is highly expressed in many NEOPLASMS.Antigens, CD13: Zinc-binding metalloproteases that are members of the type II integral membrane metalloproteases. They are expressed by GRANULOCYTES; MONOCYTES; and their precursors as well as by various non-hematopoietic cells. They release an N-terminal amino acid from a peptide, amide or arylamide.Antigens, Protozoan: Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.T-Lymphocytes: 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.Antigens, CD86: A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.Flow Cytometry: 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.B-Lymphocytes: 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.Antigens, Polyomavirus Transforming: 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, CD95: 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.HLA Antigens: 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.Antigens, Differentiation, B-Lymphocyte: Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.Antigens, CD45: 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.Immunophenotyping: 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.NAD+ NucleosidaseAntigens, Fungal: Substances of fungal origin that have antigenic activity.Molecular Sequence Data: 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.H-2 Antigens: The major group of transplantation antigens in the mouse.Sialic Acid Binding Ig-like Lectin 3: A 67-kDa sialic acid binding lectin that is specific for MYELOID CELLS and MONOCYTE-MACROPHAGE PRECURSOR CELLS. This protein is the smallest siglec subtype and contains a single immunoglobulin C2-set domain. It may play a role in intracellular signaling via its interaction with SHP-1 PROTEIN-TYROSINE PHOSPHATASE and SHP-2 PROTEIN-TYROSINE PHOSPHATASE.Antigens, Helminth: Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.Receptors, Antigen, T-Cell: 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.Antigens, CD18: Cell-surface glycoprotein beta-chains that are non-covalently linked to specific alpha-chains of the CD11 family of leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE-ADHESION). A defect in the gene encoding CD18 causes LEUKOCYTE-ADHESION DEFICIENCY SYNDROME.Lymphocyte Activation: 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.Antigens, CD30: A member of the tumor necrosis factor receptor superfamily that may play a role in the regulation of NF-KAPPA B and APOPTOSIS. They are found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; NEUTROPHILS; EOSINOPHILS; MAST CELLS and NK CELLS. Overexpression of CD30 antigen in hematopoietic malignancies make the antigen clinically useful as a biological tumor marker. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.CD8-Positive T-Lymphocytes: 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.Epitopes: Sites on an antigen that interact with specific antibodies.Antigens, CD9: A subtype of tetraspanin proteins that play a role in cell adhesion, cell motility, and tumor metastasis. CD9 antigens take part in the process of platelet activation and aggregation, the formation of paranodal junctions in neuronal tissue, and the fusion of sperm with egg.Carcinoembryonic Antigen: 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.HLA-DR Antigens: 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.Antigens, CD15: 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, Viral, Tumor: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Antigens, CD43: A sialic acid-rich protein and an integral cell membrane mucin. It plays an important role in activation of T-LYMPHOCYTES.Antigens, CD36: Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.Amino Acid Sequence: 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.Antigens, CD11: A group of three different alpha chains (CD11a, CD11b, CD11c) that are associated with an invariant CD18 beta chain (ANTIGENS, CD18). The three resulting leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE ADHESION) are LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; MACROPHAGE-1 ANTIGEN; and ANTIGEN, P150,95.Histocompatibility Antigens Class II: 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.Histocompatibility Antigens: 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.Antigens, CD59: Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)Receptors, Antigen, B-Cell: 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.Proliferating Cell Nuclear Antigen: 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.Antigens, CD57: Oligosaccharide antigenic determinants found principally on NK cells and T-cells. Their role in the immune response is poorly understood.Antigens, CD70: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds to CD27 ANTIGEN. It is found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS where it plays a role in stimulating the proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES.Antigens, CD46: A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.Lectins, C-Type: A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.Antigens, CD58: Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on macrophages. CD58 mediates cell adhesion by binding to CD2; (ANTIGENS, CD2); and this enhances antigen-specific T-cell activation.Antigens, CD4: 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.Antigens, CD47: A ubiquitously expressed membrane glycoprotein. It interacts with a variety of INTEGRINS and mediates responses to EXTRACELLULAR MATRIX PROTEINS.Antigens, CD11b: A CD antigen that contains a conserved I domain which is involved in ligand binding. When combined with CD18 the two subunits form MACROPHAGE-1 ANTIGEN.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Prostate-Specific Antigen: 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.Antigens, CD11c: An integrin alpha subunit of approximately 150-kDa molecular weight. It is expressed at high levels on monocytes and combines with CD18 ANTIGEN to form the cell surface receptor INTEGRIN ALPHAXBETA2. The subunit contains a conserved I-domain which is characteristic of several of alpha integrins.O Antigens: 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)HLA-A2 Antigen: A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.Enzyme-Linked Immunosorbent Assay: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.CD4 Lymphocyte Count: The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Cell SeparationAntigens, Tumor-Associated, Carbohydrate: 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.Antigens, CD55: GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.Antigens, CD31: Cell adhesion molecules present on virtually all monocytes, platelets, and granulocytes. CD31 is highly expressed on endothelial cells and concentrated at the junctions between them.Tumor Cells, Cultured: 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.Histocompatibility Antigens Class I: 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.Antigens, CD81: Tetraspanin proteins that are involved in a variety of cellular functions including BASEMENT MEMBRANE assembly, and in the formation of a molecular complexes on the surface of LYMPHOCYTES.Cells, Cultured: 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.Antigens, CD137: A member of the tumor necrosis factor receptor superfamily that is specific for 4-1BB LIGAND. It is found in a variety of immune cell types including activated T-LYMPHOCYTES; NATURAL KILLER CELLS; and DENDRITIC CELLS. Activation of the receptor on T-LYMPHOCYTES plays a role in their expansion, production of cytokines and survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Lymphocytes: 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.Mice, Inbred BALB CMonocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.HLA-A Antigens: 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.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Dendritic Cells: 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).Receptors, Interleukin-2: Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.Blood Group Antigens: Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.Hepatitis B Surface Antigens: 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.Antigens, CD63: Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Antibody Specificity: 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.Antigens, CD151: Tetraspanin proteins found associated with LAMININ-binding INTEGRINS. The CD151 antigens may play a role in the regulation of CELL MOTILITY.Antigens, CD79: 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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Fluorescent Antibody Technique: 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.HLA-D Antigens: 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.CD30 Ligand: A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. It may play a role in INFLAMMATION and immune regulation.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.N-Glycosyl Hydrolases: A class of enzymes involved in the hydrolysis of the N-glycosidic bond of nitrogen-linked sugars.Burkitt Lymphoma: 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.Receptors, Antigen: Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.Immunization: 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).Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Antigens, CD11a: An alpha-integrin subunit found on lymphocytes, granulocytes, macrophages and monocytes. It combines with the integrin beta2 subunit (CD18 ANTIGEN) to form LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1.RNA, Messenger: 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.Hepatitis B Antigens: 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.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Immune Sera: 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.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Mice, SCID: Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.T-Lymphocytes, Cytotoxic: 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.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Antigen-Presenting 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.Herpesvirus 4, Human: 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.Receptors, Antigen, T-Cell, alpha-beta: 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.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.HLA-B Antigens: 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.Immunologic Memory: 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.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Cytotoxicity, Immunologic: 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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.MART-1 Antigen: 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, CD147: A widely distributed cell surface transmembrane glycoprotein that stimulates the synthesis of MATRIX METALLOPROTEINASES. It is found at high levels on the surface of malignant NEOPLASMS and may play a role as a mediator of malignant cell behavior.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Mice, Inbred C57BLOvalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.HIV Antigens: 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.CTLA-4 Antigen: 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.HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)Antigens, CD82: A widely expressed transmembrane glycoprotein that functions as a METASTASIS suppressor protein. It is underexpressed in a variety of human NEOPLASMS.Immunoenzyme Techniques: 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.Antibodies: 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).Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Antigens, Thy-1: 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.Cytokines: 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.Immune Tolerance: 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.Immunity, Cellular: 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.Thymus Gland: 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.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Clone Cells: 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)Epstein-Barr Virus Nuclear Antigens: Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Immunoglobulin M: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.H-Y Antigen: 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.Antigens, CD146: A cell adhesion molecule of the immunoglobulin superfamily that is expressed in ENDOTHELIAL CELLS and is involved in INTERCELLULAR JUNCTIONS.Antigens, Heterophile: Antigens stimulating the formation of, or combining with heterophile antibodies. They are cross-reacting antigens found in phylogenetically unrelated species.T-Lymphocytes, Regulatory: CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.Antibodies, Monoclonal, Murine-Derived: Antibodies obtained from a single clone of cells grown in mice or rats.Epitopes, T-Lymphocyte: Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.Interferon-gamma: 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.Antigens, CD98: A heterodimeric protein that is a cell surface antigen associated with lymphocyte activation. The initial characterization of this protein revealed one identifiable heavy chain (ANTIGENS, CD98 HEAVY CHAIN) and an indeterminate smaller light chain. It is now known that a variety of light chain subunits (ANTIGENS, CD98 LIGHT CHAINS) can dimerize with the heavy chain. Depending upon its light chain composition a diverse array of functions can be found for this protein. Functions include: type L amino acid transport, type y+L amino acid transport and regulation of cellular fusion.Hepatitis B Core Antigens: The hepatitis B antigen within the core of the Dane particle, the infectious hepatitis virion.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Antigen-Antibody Complex: 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.Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.Molecular Weight: The sum of the weight of all the atoms in a molecule.Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.HLA-DQ Antigens: 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.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Signal Transduction: 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.Mice, Inbred Strains: 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.Forssman Antigen: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Rabbits: 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.Antigens, CD274: An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.Complement Fixation Tests: Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.Simian virus 40: A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Adjuvants, Immunologic: 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.Isoantigens: Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.Hybridomas: 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.gp100 Melanoma Antigen: A melanosome-associated protein that plays a role in the maturation of the MELANOSOME.Major Histocompatibility Complex: 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.Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.

Skeletal muscle type ryanodine receptor is involved in calcium signaling in human B lymphocytes. (1/892)

The regulation of intracellular free Ca2+ concentration ([Ca2+]i) in B cells remains poorly understood and is presently explained almost solely by inositol 1,4,5-triphosphate (IP3)-mediated Ca2+ release, followed by activation of a store-operated channel mechanism. In fact, there are reports indicating that IP3 production does not always correlate with the magnitude of Ca2+ release. We demonstrate here that human B cells express a ryanodine receptor (RYR) that functions as a Ca2+ release channel during the B cell antigen receptor (BCR)-stimulated Ca2+ signaling process. Immunoblotting studies showed that both human primary CD19(+) B and DAKIKI cells express a 565-kDa immunoreactive protein that is indistinguishable in molecular size and immunoreactivity from the RYR. Selective reverse transcription-polymerase chain reaction, restriction fragment length polymorphism, and sequencing of cloned cDNA indicated that the major isoform of the RYR expressed in primary CD19(+) B and DAKIKI cells is identical to the skeletal muscle type (RYR1). Saturation analysis of [3H]ryanodine binding yielded Bmax = 150 fmol/mg of protein and Kd = 110 nM in DAKIKI cells. In fluo-3-loaded CD19(+) B and DAKIKI cells, 4-chloro-m-cresol, a potent activator of Ca2+ release mediated by the ryanodine-sensitive Ca2+ release channel, induced Ca2+ release in a dose-dependent and ryanodine-sensitive fashion. Furthermore, BCR-mediated Ca2+ release in CD19(+) B cells was significantly altered by 4-chloro-m-cresol and ryanodine. These results indicate that RYR1 functions as a Ca2+ release channel during BCR-stimulated Ca2+ signaling and suggest that complex Ca2+ signals that control the cellular activities of B cells may be generated by cooperation of the IP3 receptor and RYR1.  (+info)

Increased expression of regeneration and tolerance factor in individuals with human immunodeficiency virus infection. (2/892)

Regeneration and tolerance factor (RTF) plays a pivotal role in successful pregnancy outcome and has potent immunomodulating properties. During pregnancy, it is abundantly expressed in the placenta and on peripheral B lymphocytes. Several lines of evidence suggest that both successful pregnancy outcome and progression from human immunodeficiency virus (HIV) infection to AIDS are associated with a Th2-type response. As a result, we hypothesized that the cellular expression of RTF may also be increased during infection with HIV. Using flow cytometric analysis, we showed a significantly (P < 0.01) increased expression of RTF on CD3(+) cells obtained from individuals with HIV over that for individuals without HIV. On average, 32.1% of the CD3(+) cells from individuals with HIV expressed high levels of RTF. In contrast, an average of only 6.7% of the CD3(+) cells from individuals without HIV expressed high levels of RTF. Similar results were obtained when CD19(+) cells from individuals with (mean, 44.1%) and without (mean, 25.8%) HIV were evaluated. Linear regression analysis suggested that high levels of RTF expression by CD3(+) cells correlated better with viral load (r value, 0.46) than with absolute CD4 count (r value, 0.09). While additional experiments are necessary to delineate the precise immunologic role of RTF, our current data suggest that RTF expression during HIV infection may be a useful marker of immune activation.  (+info)

Predictive value of CD19 measurements for bacterial infections in children infected with human immunodeficiency virus. (3/892)

We investigated the predictive value of CD19 cell percentages (CD19%) for times to bacterial infections, using data from six pediatric AIDS Clinical Trials Group protocols and adjusting for other potentially prognostic variables, such as CD4%, CD8%, immunoglobulin (IgA) level, lymphocyte count, prior infections, prior zidovudine treatment, and age. In addition, we explored the combined effects of CD19% and IgG level in predicting time to infection. We found that a low CD19% is associated with a nonsignificant 1.2-fold increase in hazard of bacterial infection (95% confidence interval: 0.97, 1.49). In contrast, a high IgG level is associated with a nonsignificant 0.87-fold decrease in hazard of infection (95% confidence interval: 0.68, 1.12). CD4% was more prognostic of time to bacterial infection than CD19% or IgG level. Low CD19% and high IgG levels together lead to a significant (P < 0. 01) 0.50-fold decrease in hazard (95% confidence interval: 0.35, 0. 73) relative to low CD19% and low IgG levels. Similarly, in a model involving assay result changes (from baseline to 6 months) as well as baseline values, the effect of CD19% by itself is reversed from its effect in conjunction with IgG. In this model, CD19% that are increasing and high are associated with decreases in hazard of infection (P < 0.01), while increasing CD19% and increasing IgG levels are associated with significant (at the P = 0.01 level) fourfold increases in hazard of infection relative to stable CD19% and decreasing, stable, or increasing IgG levels. Our data suggest that CD19%, in conjunction with IgG level, provides a useful prognostic tool for bacterial infections. It is highly likely that T-helper function impacts on B-cell function; thus, inclusion of CD4% in such analyses may greatly enhance the assessment of risk for bacterial infection.  (+info)

Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma. (4/892)

Fetal CD34(+) CD38(+) cells have recently been found to persist in maternal peripheral blood for many years after pregnancy. CD34(+) CD38(+) cells are progenitor cells that can differentiate into mature immune-competent cells. We asked whether long-term fetal microchimerism occurs in T lymphocyte, B lymphocyte, monocyte, and natural-killer cell populations of previously pregnant women. We targeted women with sons and used polymerase chain reaction for a Y-chromosome-specific sequence to test DNA extracted from peripheral blood mononuclear cells (PBMC) and from CD3, CD19, CD14, and CD56/16 sorted subsets. We also asked whether persistent microchimerism might contribute to subsequent autoimmune disease in the mother and included women with the autoimmune disease scleroderma. Scleroderma has a peak incidence in women after childbearing years and has clinical similarities to chronic graft-versus-host disease that occurs after allogeneic hematopoietic stem-cell transplantation, known to involve chimerism. Sixty-eight parous women were studied for male DNA in PBMC and 20 for PBMC subsets. Microchimerism was found in PBMC from 33% (16 of 48) of healthy women and 60% (12 of 20) women with scleroderma, P =.046. Microchimerism was found in some women in CD3, CD19, CD14, and CD56/16 subsets including up to 38 years after pregnancy. Microchimerism in PBMC subsets was not appreciably more frequent in scleroderma patients than in healthy controls. Overall, microchimerism was found in CD3, CD19, and CD14 subsets in approximately one third of women and in CD56/16 in one half of women. HLA typing of mothers and sons indicated that HLA compatibility was not a requirement for persistent microchimerism in PBMC subsets. Fetal microchimerism in the face of HLA disparity implies that specific maternal immunoregulatory pathways exist that permit persistence but prevent effector function of these cells in normal women. Although microchimerism in PBMC was more frequent in women with scleroderma than healthy controls additional studies will be necessary to determine whether microchimerism plays a role in the pathogenesis of this or other autoimmune diseases.  (+info)

Cutting edge: recruitment of the CD19/CD21 coreceptor to B cell antigen receptor is required for antigen-mediated expression of Bcl-2 by resting and cycling hen egg lysozyme transgenic B cells. (5/892)

Recruitment of the CD19/CD21 coreceptor is thought to lower the threshold for effective signaling through the B cell Ag receptor. We provide evidence supporting a second role for coreceptor recruitment, and that is to enhance the survival/proliferative potential of the responding B cells. We show that B cell Ag receptor signaling in the absence of coreceptor recruitment induces cellular accumulation of the anti-apoptotic protein Bcl-xL, whereas CD19-mediated signals are required for Bcl-2 accumulation. The expression of both anti-apoptotic proteins correlates with the enhanced responsiveness of both resting and cycling B cells to growth-promoting signals delivered through CD40. These results provide further evidence for the necessity of coreceptor recruitment during Ag-dependent B cell activation and indicate that Ags derived from inflammatory sites function as better thymus-dependent Ags than their counterparts not coated with complement fragments.  (+info)

Phosphorylation of CD19 Y484 and Y515, and linked activation of phosphatidylinositol 3-kinase, are required for B cell antigen receptor-mediated activation of Bruton's tyrosine kinase. (6/892)

Bruton's tyrosine kinase (Btk) plays a critical role in B cell Ag receptor (BCR) signaling, as indicated by the X-linked immunodeficiency and X-linked agammaglobulinemia phenotypes of mice and men that express mutant forms of the kinase. Although Btk activity can be regulated by Src-family and Syk tyrosine kinases, and perhaps by phosphatidylinositol 3,4,5-trisphosphate, BCR-coupled signaling pathways leading to Btk activation are poorly understood. In view of previous findings that CD19 is involved in BCR-mediated phosphatidylinositol 3-kinase (PI3-K) activation, we assessed its role in Btk activation. Using a CD19 reconstituted myeloma model and CD19 gene-ablated animals we found that BCR-mediated Btk activation and phosphorylation are dependent on the expression of CD19, while BCR-mediated activation of Lyn and Syk is not. Wortmannin preincubation inhibited the BCR-mediated activation and phosphorylation of Btk. Btk activation was not rescued in the myeloma by expression of a CD19 mutant in which tyrosine residues previously shown to mediate CD19 interaction with PI3-K, Y484 and Y515, were changed to phenylalanine. Taken together, the data presented indicate that BCR aggregation-driven CD19 phosphorylation functions to promote Btk activation via recruitment and activation of PI3-K. Resultant phosphatidylinositol 3,4,5-trisphosphate probably functions to localize Btk for subsequent phosphorylation and activation by Src and Syk family kinases.  (+info)

Expression of Epstein-Barr virus BamHI-A rightward transcripts in latently infected B cells from peripheral blood. (7/892)

In addition to the Epstein-Barr virus (EBV) EBNA and LMP latency genes, there is a family of alternatively spliced BamHI-A rightward transcripts (BARTs). These latency transcripts are highly expressed in the EBV-associated malignancies nasopharyngeal carcinoma and Burkitt's lymphoma, and are expressed at lower levels in latently EBV-infected B-cell lines. The contribution of the BARTs to EBV biology or pathogenesis is unknown. Resting B cells have recently been recognized as a reservoir for EBV persistence in the peripheral blood. In these cells, EBV gene expression is tightly restricted and the only viral gene known to be consistently expressed is LMP2A. We used cell sorting and reverse-transcriptase polymerase chain reaction (RT-PCR) to examine whether BARTs are expressed in the restricted form of in vivo latency. Our results demonstrated that RNAs with splicing diagnostic for transcripts containing the BART RPMS1 and BARFO open-reading frames (ORFs) were expressed in CD19(+) but not in CD23(+) B cells isolated from peripheral blood of healthy individuals. The product of the proximal RPMS1 ORF has not previously been characterized. The RPMS1 ORF was shown to encode a 15-kD protein that localized to the nucleus of transfected cells. Expression of the BARTs in peripheral blood B cells suggests that the proteins encoded by these transcripts are likely to be important for maintenance of in vivo latency.  (+info)

Distribution of lymphocytes and adhesion molecules in human cervix and vagina. (8/892)

Knowledge of the histological distribution of leucocytes and adhesion molecules in the human genital tract is scarce although local immunity in this region is important. Using immunohistochemical methods, we here describe the organization of CD3+, CD8+ and CD4+ T cells, CD19+ B cells, CD38+ plasma cells, major histocompatibility complex (MHC) class II+ antigen-presenting cells and CD14+ monocytes, as well as the expression of endothelial addressins in normal human ecto-cervical and vaginal mucosa. T cells were clustered in a distinct band beneath the epithelium and were also dispersed in the epithelium and the lamina propria, whereas CD38+ plasma cells were present only in the lamina propria. MHC class II+ cells were numerous in the lamina propria and in the epithelium, where they morphologically resembled dendritic cells. Lymphoid aggregates containing CD19+ and CD20+ B cells as well as CD3+, CD4+ and CD8+ cells were also found in the cervix. The mucosal addressin cell adhesion molecule-1 (MAdCAM-1) was not expressed on the vascular endothelium in the cervical or vaginal mucosa. In contrast, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion protein-1 (VAP-1) and P-selectin were expressed in all tissue samples, and vascular cell adhesion molecule-1 (VCAM-1) and E-selectin were found in four of seven samples. We conclude that the distribution of leucocytes and adhesion molecules is very similar in the ecto-cervical and the vaginal mucosa and that the regulation of lymphocyte homing to the genital tract is different from that seen in the intestine. Our results also clearly suggest that the leucocytes are not randomly scattered in the tissue but organized in a distinct pattern.  (+info)

*Adoptive cell transfer

Antigen CD19 appears only on B cells, which go awry in lymphoma and leukemia. Loss of B cells can be countered with ... In 2016, CD19-specific chimeric antigen receptor (CAR)-modified T cells were used to treat patients with relapsed and ... against B cell antigen CD19 was shown to mediate regression of an advanced B cell lymphoma. In 2009, a woman given T cells ... "Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy". ...

*Blinatumomab

... specifically targets the CD19 antigen present on B cells. In December 2014 it was approved by the US Food and Drug ... A molecule of blinatumomab combines two binding sites: a CD3 site for T cells and a CD19 site for the target B cells. CD3 is ... CD3 and CD19 are expressed in both pediatric and adult patients, making blinatumomab a potential therapeutic option for both ... "CD19-/CD3-bispecific antibody of the BiTE class is far superior to tandem diabody with respect to redirected tumor cell lysis ...

*Bing-Neel syndrome

With respect to diagnosing BNS, flow cytometry analyzes CSF contents for B-cells expressing the pan antigens CD19 and CD20, ...

*CD19

Mouse CD Antigen Chart Human CD Antigen Chart Human CD19 genome location and CD19 gene details page in the UCSC Genome Browser ... CD19 CD19 molecule". Tedder TF, Isaacs CM (Jul 1989). "Isolation of cDNAs encoding the CD19 antigen of human and mouse B ... B-lymphocyte antigen CD19, also known as CD19 (Cluster of Differentiation 19), is a protein that in humans is encoded by the ... Since 2011, anti-CD19 immunotoxin treatments targeting CD19 have begun to enter trials. Most current experimental anti-CD19 ...

*B-Cell Prolymphocytic Leukemia

... b-lymphocyte surface antigens CD19, CD20, CD22, CD79a and FMC7, and weak expression of CD5 and CD23. Due to the similarities ... B-lymphocytes have two responsibilities: Production of antibodies - In response to antigens, B-lymphocytes produce and release ... one of its key identifiers is the absence in expression of the surface antigens CD10, CD11c, CD25, CD103 and cyclin D1 - an ... Interactions between antibodies and antigens allow B-lymphocytes to establish cellular memories, otherwise known as immunities ...

*Acute lymphoblastic leukemia

In this therapy, mice are immunized with the CD19 antigen and produce anti-CD19 antibodies. Hybridomas developed from mouse ... cytotoxic proteins and proliferation of T cells to kill CD19 B cells. Chimeric antigen receptors (CARs) have been developed as ... Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors ... CD19 is a molecule found on all B-cells and can be used as a means of distinguishing the potentially malignant B-cell ...

*Kite Pharma

... which a patient's T cells are genetically modified to express a chimeric antigen receptor designed to target the antigen CD19, ... which a patient's T cells are genetically modified to express a chimeric antigen receptor designed to target the antigen CD19, ... Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy, for Refractory Aggressive Non-Hodgkin's Lymphoma (NHL) ". MarketWatch ... with the NCI for the research and clinical development of a fully human anti-CD19 chimeric antigen receptor (CAR) product ...

*MALT lymphoma

B-cell-associated antigens such as CD19, CD20, CD22, and CD79a are usually expressed. In contrast to small lymphocytic lymphoma ...

*David G. Maloney

Turtle, C., Riddell, S. & Maloney, D. (2016). CD19-Targeted chimeric antigen receptor-modified T-cell immunotherapy for B-cell ... Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified ... doi:10.1002/cpt.392 Turtle, C. J., & Maloney, D. G. (2016). Clinical trials of CD19-targeted CAR-modified T cell therapy; a ... Maloney leads an early-phase clinical trial for patients with certain advanced, treatment-resistant CD19-positive B-cell ...

*List of MeSH codes (D23)

... antigens, cd15 MeSH D23.050.301.264.035.118 --- antigens, cd18 MeSH D23.050.301.264.035.119 --- antigens, cd19 MeSH D23.050. ... antigens, cd5 MeSH D23.050.301.264.051.119 --- antigens, cd19 MeSH D23.050.301.264.051.120 --- antigens, cd20 MeSH D23.050. ... antigens, cd15 MeSH D23.101.100.110.118 --- antigens, cd18 MeSH D23.101.100.110.119 --- antigens, cd19 MeSH D23.101.100.110.120 ... antigens, cd5 MeSH D23.101.100.150.119 --- antigens, cd19 MeSH D23.101.100.150.120 --- antigens, cd20 MeSH D23.101.100.150.140 ...

*Juno Therapeutics

The trials will assess combinations of MEDI4736 and one of Juno's CD19 directed chimeric antigen receptor T cell candidates. In ... In December 2014 the company signed an agreement with Opus Bio, Inc for a chimeric antigen receptor (CAR-T) cell product ... "A Pediatric and Young Adult Trial of Genetically Modified T Cells Directed Against CD19 for Relapsed/Refractory CD19+ Leukemia ... fully human binding domain targeting B-cell maturation antigen. In January 2018, Celgene announced it would acquire Juno for $9 ...

*AstraZeneca

The trials will assess combinations of MEDI4736 and one of Juno Therapeutics' CD19 directed chimeric antigen receptor T-cell ...

*Induced stem cells

Another method combines iPSC and chimeric antigen receptor (CAR) technologies to generate human T cells targeted to CD19, an ... DC-like antigen-presenting cells obtained from human induced pluripotent stem cells can serve as a source for vaccination ... Thus, the ability to generate platelet products ex vivo and platelet products lacking HLA antigens in serum-free media would ... A potentially efficient approach for generating antigen-specific CTLs is to revert mature immune T cells into iPSCs, which ...

*Tumor antigens recognized by T lymphocytes

... observed in leukemic patients infused with T cells genetically engineered to carry an artificial receptor that recognizes CD19 ... In some patients, the majority of the tumor-specific T cells recognize mutated antigens. The contribution of these antigens to ... The carcinoma cells still harbour the viral genes and antigens. As expected T cell responses against antigens encoded by genes ... Cancer therapy targeted at tumor antigens can involve the direct use of these antigens in vaccines, but also the adoptive ...

*LYN

In these cells, a small amount of LYN is associated with cell surface receptor proteins, including the B cell antigen receptor ... BCR), CD40, or CD19. The abbreviation Lyn is derived from Lck/Yes novel tyrosine kinase, Lck and Yes also being members of the ... Brown VK, Ogle EW, Burkhardt AL, Rowley RB, Bolen JB, Justement LB (Jun 1994). "Multiple components of the B cell antigen ... Yamamoto T, Yamanashi Y, Toyoshima K (Apr 1993). "Association of Src-family kinase Lyn with B-cell antigen receptor". ...

*Acute biphenotypic leukaemia

The presence of specific T-lymphoid antigens, cytoplasmic CD3 (cCD3), MPO and CD 19 became the most important standard for ...

*CD79B

... induced tyrosine phosphorylation of CD19 requires a CD19 domain that mediates association with components of the B cell antigen ... It is associated with agammaglobulinemia-6. The B lymphocyte antigen receptor is a multimeric complex that includes the antigen ... Müller B, Cooper L, Terhorst C (1995). "Interplay between the human TCR/CD3 epsilon and the B-cell antigen receptor associated ... 1994). "CD5 is associated with the human B cell antigen receptor complex". Eur. J. Immunol. 24 (4): 812-6. doi:10.1002/eji. ...

*Complement receptor 2

CD19 and CD81(=TAPA-1). The CR2-CD19-CD81 complex is often called the B cell coreceptor complex, because CR2 binds to antigens ... Complement receptor 2 has been shown to interact with CD19. Epstein-Barr virus (EBV) binds to B cells at CR2 during infection ... Horváth G, Serru V, Clay D, Billard M, Boucheix C, Rubinstein E (November 1998). "CD19 is linked to the integrin-associated ... Philadelphia: Saunders, ISBN 0-7216-0008-5 Bradbury LE, Kansas GS, Levy S, Evans RL, Tedder TF (November 1992). "The CD19/CD21 ...

*Plasma cell

Another important surface antigen is CD319 (SLAMF7). This antigen is expressed at high levels on normal human plasma cells. It ... such as CD19 and CD20. Instead, plasma cells are identified through flow cytometry by their additional expression of CD138, ... After leaving the bone marrow, the B cell acts as an antigen presenting cell (APC) and internalizes offending antigens, which ... Pieces of the antigen (which are now known as antigenic peptides) are loaded onto MHC II molecules, and presented on its ...

*Chimeric antigen receptor

The first two FDA approved CAR-T therapies were targeted at CD19 (found on many types of lymphoma cells). The approved ... A spacer region links the antigen binding domain to the transmembrane domain. It should be flexible enough to allow the antigen ... Bridgeman, JS; Hawkins RE; Bagley S; Blaylock M; Holland M; Gilham DE (2010). "The Optimal Antigen Response of Chimeric Antigen ... A list of tumors antigens and CARs in in vitro and in vivo trials A list of tumors antigens and CARs in in vitro and in vivo ...

*Co-stimulation

... is required in addition to the antigen-specific signal from their antigen receptors. T cells require two signals ... CR2 on mature B cells forms a complex with CD19 and CD81. This complex is called the B cell coreceptor complex for such ... B cell binds antigens with its BCR (a membrane-bound antibody), which transfers intracellular signals to the B cell as well as ... The latter case induces recognition by antigen-specific Th2 cells, leading to activation of the B cell through binding of TCR ...

*Fuat Oduncu

A recombinant triplebody with specificity for CD19 and HLA-DR mediates preferential binding to antigen double-positive cells by ... These molecules present antibody-derivatives and small molecules which specifically bind to the surface antigens of cancer ... A Novel CD19-directed recombinant bispecific antibody derivative with enhanced immune effector functions for human leukemic ... A dual-targeting triplebody mediates preferential redirected lysis of antigen double-positive over single-positive leukemic ...

*Biochemical cascade

CD28/CD19) play an important role because they can improve the antigen/receptor binding and initiate parallel cascade events, ... These receptors, that recognize the antigen soluble (B cells) or linked to a molecule on Antigen Presenting Cells (T cells), ... The antigen receptor and signal protein form a stable complex, named BCR or TCR, in B or T cells, respectively. The family Src ... Therefore, Lyn and Lck, in lymphocytes B and T, respectively, phosphorylate ITAMs after the antigen recognition and the ...

*Cancer immunotherapy

Dendritic cells are antigen presenting cells (APCs) in the mammalian immune system. In cancer treatment they aid cancer antigen ... This treatment cleans CD19 positive cells from the body (including the disease). Antibodies are a key component of the adaptive ... Cancer vaccine Antigen 5T4 Chimeric antigen receptor Coley's Toxins Combinatorial ablation and immunotherapy Cryoimmunotherapy ... Antigens can be added to the antibody and can induce the dendritic cells to mature and provide immunity to the tumor. Dendritic ...

*B cell

... and signals are transduced through CD19 and CD81 to lower the activation threshold of the cell. Antigens that activate B cells ... Antigens that activate B cells without T cell help are known as T cell-independent (TI) antigens and include foreign ... As with TD antigens, B cells activated by TI antigens need additional signals to complete activation, but instead of receiving ... Upon antigen binding, the memory B cell takes up the antigen through receptor-mediated endocytosis, degrades it, and presents ...

*CD34

Antigens, CD34 at the US National Library of Medicine Medical Subject Headings (MeSH) Mouse CD Antigen Chart Human CD Antigen ... Hotfilder M, Röttgers S, Rosemann A, Jürgens H, Harbott J, Vormoor J (Jul 2002). "Immature CD34+CD19- progenitor/stem cells in ... Hematopoietic progenitor cell antigen CD34 also known as CD34 antigen is a protein that in humans is encoded by the CD34 gene. ... A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells". Journal of ...
CD19-specific chimeric antigen receptor (CAR)-modified T cells have antitumor activity in B cell malignancies, but factors that affect toxicity and efficacy have been difficult to define because of differences in lymphodepletion and heterogeneity of CAR-T cells administered to individual patients. We conducted a clinical trial in which CD19 CAR-T cells were manufactured from defined T cell subsets and administered in a 1:1 CD4+/CD8+ ratio of CAR-T cells to 32 adults with relapsed and/or refractory B cell non-Hodgkins lymphoma after cyclophosphamide (Cy)-based lymphodepletion chemotherapy with or without fludarabine (Flu). Patients who received Cy/Flu lymphodepletion had increased CAR-T cell expansion and persistence, and higher response rates [50% complete remission (CR), 72% overall response rate (ORR)] than patients who received Cy-based lymphodepletion without Flu (8% CR, 50% ORR). The CR rate in patients treated with Cy/Flu at the maximally tolerated dose was 64% (82% ORR; n = 11). Cy/Flu ...
The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a 5T4 monoclonal antibody, conferring specific immunity against 5T4 positive cells.
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
BACKGROUND. Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS. We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being ...
Human immunodeficiency virus (HIV) is a causative agent of acquired immune deficiency syndrome (AIDS). Highly active antiretroviral therapy (HAART) can slow down the replication of HIV-1, leading to an improvement in the survival of HIV-1-infected patients. However, drug toxicities and poor drug administration has led to the emergence of a drug-resistant strain. HIV-1 immunotherapy has been continuously developed, but antibody therapy and HIV vaccines take time to improve its efficiency and have limitations. HIV-1-specific chimeric antigen receptor (CAR)-based immunotherapy founded on neutralizing antibodies is now being developed. In HIV-1 therapy, anti-HIV chimeric antigen receptors showed promising data in the suppression of HIV-1 replication; however, autologous transfusion is still a problem. This has led to the development of effective peptides and proteins for an alternative HIV-1 treatment. In this paper, we provide a comprehensive review of potent anti-HIV-1 peptides and proteins that reveal
The CD19 CAR Detection Reagent (Biotin) has been developed for the detection of transduced T cells that are engineered to express CD19-specific chimeric antigen receptors (CAR) on the cell surface, which recognize human CD19 antigen. The CD19 CAR Detection Reagent (Biotin) is an antigen based detection reagent conjugated to biotin. It contains a recombinantly expressed fusion protein consisting of the human CD19 extracellular domains and a specifically mutated human IgG1 Fc region. The engineered CD19 CAR T cells can be detected via the recognition of the CD19 protein, and identified by flow cytometry via anti-biotin fluorochromes. The mutated human IgG1 Fc region of the CD19 CAR Detection Reagent abolishes their binding to Fcγ receptors. This allows for background-free analysis and eliminates the need for additional blocking steps, such as using a FcR blocking reagent. - Ireland
PURPOSE OF REVIEW: As T cells engineered with chimeric antigen receptors (CARs) are entering advanced phases of clinical trial testing with promising results, the potential implications of use in an allogeneic environment are emerging as an important consideration. This review discusses the use of allogeneic CAR therapy, the potential effects of T-cell receptor (TCR) signaling on CAR T-cell efficacy, and the potential for TCR elimination to generate an off-the-shelf product. RECENT FINDINGS: The majority of preclinical and clinical data regarding allogeneic T cells are focused on safety of their use given the potential for graft-versus-host disease (GVHD) mediated by the T-cell receptor expressed with the introduced CAR ...
Be that as it may, CAR T-cell therapy cant exist alone since T cells are generally combined with patient preconditioning as chemotherapy or systemic cytokine, which is related to toxicity. Thus, complete CAR T-cell treatment not only includes the well-known elements but also includes the CAR T cell with largely unknown toxicity. In terms of the latest report of side effects of CAR T-cell therapy, current preclinical animal tests of CAR T-cells may not be suitable for the analysis of CAR T-cell toxicity profiling. Therefore, CAR T cell validation is explored in the use of preclinical models to examine its potential to predict the possible toxicities driven by CAR T-cell.. Generally, most of preclinical trials on CAR T-cell function mainly discuss specificity verification and potency of antitumor activity. The specificity of CAR T-cell has been proved through in vitro assays that T cells with a specific CAR exhibit a different functional response between target antigens and nonspecific antigens. ...
As of 2015, a Dodge Hemi can be purchased at Dodge, Cars.com and AutoTrader. The label Hemi refers to the engine type and not a specific car model. Currently there are two Dodge vehicles with a Hemi,...
How can I relabel a graph or pie chart in excel 2010 so that it has the name of the color of the data(color of specific car sold) instead of the numbers(1,2,3etc) It is a graph and pie chart that is associated with the formulas in the cells and the numbers associated with it ...
Title:Chimeric Antigen Receptor T Cell Based Immunotherapy for Cancer. VOLUME: 13 ISSUE: 5. Author(s):Feng Li, Tengfei Zhang, Ling Cao and Yi Zhang*. Affiliation:Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan. Keywords:Cancer immunotherapy, CAR T cells, hematologic malignancies, solid tumor, cancer cells, leukemia.. Abstract:Cancer immunotherapy, a new weapon against cancers by harnessing the patients own immune system, potentiates an extended remission and possibly a cure for cancer. 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. CD19 is extensively ...
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. We report long-term results from three clinical trials to evaluate gammaretroviral vector-engineered T cells for HIV. The vector encoded a chimeric antigen receptor (CAR) composed of CD4 linked to the CD3ζ signaling chain (CD4ζ). CAR T cells were detected in 98% of samples tested for at least 11 years after infusion at frequencies that exceeded average T cell levels after most vaccine approaches. The CD4ζ transgene retained expression and function. There was no evidence of vector-induced immortalization of cells; integration site distributions showed no evidence of persistent clonal expansion or enrichment for integration sites near genes implicated in growth control or transformation. The CD4ζ T cells had stable levels of engraftment, with decay half-lives that exceeded 16 years, in marked contrast to previous trials testing engineered T cells. ...
Background T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined....
General structure of Chimeric Antigen Receptor T tagged: molecular pathology, cancer, tcr, cd28, til, cancer immunotherapy, immunotherapy, tumor infiltrating lymphocytes, scfv, itam, immune response, cd3, powerpoint, slide
CC Grand Rounds (1) Treating Hematologic Malignancies with Chimeric Antigen Receptor T Cells and (2) Human Papilloma Virus (HPV)-Targeted T Cell Therapy for Patients with HPV-Associated Cancers
Comments, concepts and statistics about Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS.
Shanghai Youkadi Biomedical Technology is developing chimeric antigen receptor T (CAR-T) cell therapeutics for the treatment of central nervous system B-cell
The blood cells of cancer patients, reprogrammed by doctors to attack their leukemia and re-infused back into the patients veins, led to complete remissions in 27 of 30 people. Thats especially exciting because those patients had failed all conventional treatments. Not all of the remissions lasted. Nineteen patients in the study remain in remission 2 to 24 months later, and 15 of them didnt need any additional treatment. Seven patients relapsed between 6 months and 9 months after their infusion; those included three people whose cancers spread beyond the blood cells the new treatment targets. Five patients left the study for alternative therapy. The numbers are remarkable because these patients had cancer return as many as four times before they joined the study, including some whose cancer had returned after stem cell transplants. For this method, the researchers harvest a patients T cells using a process like blood transfusion. Then the lab [performs] a gene transfer, to teach the T cells ...
Chimeric antigen receptor (CAR)-T cell therapy harnesses the power of the patients own immune system to combat cancer. In theory, CAR-T cell therapy is simple; extract the patients own T-cells, modify them with a viral vector to express an artificial chimeric receptor specific for a cancer antigen, and re-infuse the cells back into the patient. […]. [Read More] ...
Is immunotherapy with chimeric antigen receptor (CAR)-directed T cells the next big thing in oncology? Presentations and discussion at a recent conference suggest the technology has considerable pro
Production of chimeric antigen receptor (CAR) T-cells involve genetically modifying the patients own T-cells, and these cells have been shown to be effective to treat to multiple types of cancer. However, the success of the first procedural step-collecting the patients own lymphocytes using apheresis-often determines the success of this promising new therapy. A study recently […]. [Read More] ...
At the forefront of medicine, Gene Therapy brings you the latest research into genetic and cell-based technologies to treat disease. It also publishes Progress & Prospects reviews and News and Commentary articles, which highlight the cutting edge of the field.
Clinical trial for Lymphocytic Leukemia | Acute | Non-Hodgkins Lymphoma | B-Cell | Leukemia | B-Cell Lymphoma | Chronic | Chronic Lymphocytic Leukemia | childhood ALL | Lymphoma , CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies
Correction: In Vitro Pre-Clinical Validation of Suicide Gene Modified Anti-CD33 Redirected Chimeric Antigen Receptor T-Cells for Acute Myeloid Leukemia.
Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy Christine E. Brown, Ph.D., Darya Alizadeh, Ph.D., Renate Starr, M.S., Lihong Weng, M.D., Jamie R. Wagner, B.A., Araceli Naranjo, B.A., Julie R. Ostberg, Ph.D., M. Suzette Blanchard, Ph.D., Julie Kilpatrick, M.S.N., Jennifer Simpson, B.A., Anita Kurien, M.B.S., Saul J. Priceman, Ph.D., Xiuli Wang, M.D., Ph.D., Todd…
On August 30th, 2017, the FDA approved the first CAR T-Cell Therapy, Kymriah™, for children and young adults up to age 25 with B-cell Acute Lymphocytic Leukemia that is refractory or in second or greater relapse. There has been an urgent need for novel treatment options that improve outcomes for patients with relapsed or refractory (r/r) B-cell precursor ALL, whose prognosis is poor. Patients often undergo multiple treatments including chemotherapy, radiation, targeted therapy or stem cell transplant, yet less than 10% of patients survive five years.. The FDA approval of Kymriah™ is based on the results of the pivotal open-label, multicenter, single-arm Phase II ELIANA trial, the first pediatric global CAR-T cell therapy registration trial, examining patients in 25 centers in the US, EU, Canada, Australia and Japan. In this study, 68 patients were infused and 63 were evaluable for efficacy. Results show 83% of patients who received treatment with Kymriah™ achieved complete remission or ...
While adoptive cell transfer (ACT) using chimeric antigen receptor-expressing (CAR) T cells has led to remarkable complete responses in leukemia, complete responses of solid tumors in patients are few. Similarly, previous investigations in mice have demonstrated clearance of large burdens of disseminated cancer using CAR T cells, but large solid tumors (,1 cm2) have not responded fully. Here we report the generation of transgenic mice containing dual specific CAR T cells with specificity for Her2 and the melanoma-associated antigen pMEL (gp100), designated CARaMEL mice. In response to Her2-positive cancer cells, T cells from CARaMEL mice could secrete cytokines and engage in cytolysis mediated by an anti-Her2 CAR. Through their endogenous TCR, CARaMEL T cells could proliferate extensively in response to gp100. We demonstrate the ability of CARaMEL T cells in ACT incorporating vaccination (ACTIV) therapy to induce eradication of large tumors of various histologies, including orthotopic breast ...
CAR T細胞免疫療法也並非是完美的療法,須注意的是「細胞因子風暴(免疫風暴)」,其為此療法在臨床應上最主要的不良反應。此風暴產生的原因是當CAR-T細胞在殺死癌細胞時,會釋放許多蛋白(即:細胞因子),其作用是啟動更多的...
News Analysis Love in the Scientific Literature There are countless ways for scientists to say, "I love you." Naming a slime-mold beetle after your wife (and another after your ex-wife) is, apparently, one of them. ...
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Carmakers release new models every year with advanced technology to attract consumer interest and to satisfy increasingly stringent government regulations. Some of these technologies are firsts or leading-edge, and they start trends that more companies will soon follow. Snapshots of the direction of the automotive industry, along with OEM and supplier perspectives, are presented in these articles that have been collected by the Editors of Automotive Engineering whose aim is to provide the reader with a complete overview of the key advances that took place over the course of one model year. • Provides a single source for information on the key engineering trends of one year. • Allows the reader to skip to chapters that cover specific car models that interest them, or read about all models from beginning to end. • Includes plenty of big, full-color images and the facts about the most recent technology and engineering innovations ...
The research team recruited 15 patients for this trial who had either relapsed or never responded to CD19-targeted CAR-T therapy, which involves extracting a population of T cells from patients and adapting them with a chimeric antigen receptor so they would target a protein commonly found on the surface of leukemia cells. Ten of them had relapsed, with their cancer cells no longer expressing CD19.. After stepping up the dose from the first round, the researchers achieved remission in 11 of the 15 patients - a remarkable 73%. The remissions lasted a median of 6 months with one patient in remission at 21 months, with signs that the cancer cells were able to mutate to stop expressing CD22 and escape the therapeutic assault.. "The take-home message is that weve found another CAR T-cell therapy that displays high-level activity in this Phase I trial," said Stanfords Crystal Mackall, who led the study. "But the relapse rate was also high. So this forces the field to get even more sophisticated. How ...
In high-risk patients with chronic lymphocytic leukemia (CLL), CD19 chimeric antigen receptor (CAR)-T cells of defined composition can be administered with an acceptable early toxicity.
Chinese doctors have reported success with a new type of immunotherapy for multiple myeloma*, a blood cancer: 33 out of 35 patients in a clinical trial had clinical remission within two months. The researchers used a type of T cell called "chimeric antigen receptor (CAR) T."** In a phase I clinical trial in China, the patients own T cells were collected, genetically reprogrammed in a lab, and injected back into the patient. The reprogramming involved inserting an artificially designed gene… read more. ...
Chinese doctors have reported success with a new type of immunotherapy for multiple myeloma*, a blood cancer: 33 out of 35 patients in a clinical trial had clinical remission within two months. The researchers used a type of T cell called "chimeric antigen receptor (CAR) T."** In a phase I clinical trial in China, the patients own T cells were collected, genetically reprogrammed in a lab, and injected back into the patient. The reprogramming involved inserting an artificially designed gene… read more. ...
While buysiders do not expect any sector-moving milestones in the wake of a catalyst-heavy third quarter, they will have at least 21 Phase III milestones and 23 PDUFA dates on their radar. But the biggest milestones on their minds are commercial milestones: the launches of chimeric antigen receptor T cell (CAR T) therapies Kymriah tisagenlecleucel from Novartis AG and Gilead Sciences Inc.s newly acquired axicabtagene ciloleucel.
CARsgen Therapeutics (CARsgen), a global pioneer focused on developing chimeric antigen receptor T-cell (CAR-T cell) therapies for solid tumors, today announced it has become the active
... antigen expressed by neuroblastoma tumor cells and treated patients with this disease. extended, low-level persistence in patients, and such persistence was associated with longer survival. This study is registered at www.clinialtrials.gov as #"type":"clinical-trial","attrs":"text":"NCT00085930″,"term_id":"NCT00085930″NCT00085930. Introduction Adoptively transferred T cells Rabbit Polyclonal to ZADH2 can recognize tumor-associated antigens presented in association with MHC molecules on the cell surface. However, many cancer cells and solid tumors have defects in antigen processing and presentation,1,2 including down-regulation of and/or failure to express MHC molecules.3,4 Introducing tumor-specific chimeric antigen receptors (CARs) into adoptively transferred T cells allows them to recognize tumor-associated antigens in an Resminostat hydrochloride manufacture MHC-independent manner while retaining their ...
In the past decade, the suppressive effects, mainly through the secretion of IL-10, of regulatory B cells on inflammatory responses have been reported in a variety of immune disorders (33-36). Additionally, immune regulation through the interaction of immune cells with the intrinsic phenotype of regulatory B cells (e.g., CD1dhiCD5+, T2-MZP, Tim-1+, and CD9+) were demonstrated in various diseases, and it plays a critical role in autoimmune diseases (37). In recent studies, functional studies in cancer diseases are emerging (38-40). In particular, the change of the distribution of regulatory B cells in cancer tissue is considered to one of important indicators (8-10). Emerging evidence suggests that regulatory B cells suppress effector immune cells including IFN-γ-producing cytotoxicity cells in various cancer diseases through the secretion of IL-10 (11). Although regulatory B cells have to play the suppressive role on the effector function of T cells in autoimmune diseases to cure diseases (41), ...
Background: Despite the success of anti-CD19 chimeric antigen receptor (CAR) therapy for relapsed/refractory ALL, not all respond and CD19-negative escape has been observed. To overcome this problem and to test an alternative target, we developed an anti-CD22 CAR. Widely expressed on B-lineage leukemia and lymphomas, CD22 represents an ideal target. The primary objectives of this phase I dose escalation study were to determine the feasibility of producing anti-CD22 CAR cells and to assess the safety of administering escalating doses of anti-CD22-CAR T cells in children and young adults with relapsed or refractory CD22+ B cell malignancies. Secondary objectives include determination of anti-leukemia effects, measurement of persistence of anti-CD22 CAR T cells, and evaluation of cytokine profiles. We report interim results based on the first 9 enrolled subjects in this first-in-human testing of anti-CD22 CAR therapy.. Design: Children and young adults with relapsed/refractory CD22+ hematologic ...
The invention describes a CAR which recognizes CD30 as a target antigen and initiates lysis of CD30-positive (CD30+) tumor cells but not of CD30+ healthy cells like hematopoietic stem cells. Specific genetic modifications of the anti-CD30 CAR ensure the specific targeting of CD30+ tumor cells and prevent unwanted side-effects. 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. In vivo experiments provided evidence that the treatment with anti-CD30 T-cells has no unwanted impact on the endogenous immune system. Thus, the CAR is most suitable for clinical application in targeting CD30+ leukemia and lymphoma cells. A clinical study phase I is planned for early 2016, indication: cutaneous T-cell lymphoma.. ...
Genetically engineered T Cell Receptors specific against cancer specific antigens, called Chimeric Antigen Receptors (CARs)[194], are extremely promising and several companies, including Juno Therapeutics, Kite Pharma and Novartis are competing to provide the first marketable solution[195]. This competition has reached extents, that it is sometimes called the CAR T-Cell Race[196]. The promise is huge, as immunotherapy often is the last rescue if all current therapies have failed. The FDA recognized this and awarded the first breakthrough therapy designation to the new drug approval (NDA) filling for CTL019, the anti-CD19 chimeric antigen receptor T-cell therapy developed at the University of Pennsylvania on July 1, 2014[197]. CARs will reprogram the human immune system to specifically recognize cancer cell surface markers and launch an immune response against the tumor cells. In most cases, CD8+ Killer T Cells are equipped with the CARs, but current clinical trails are exploring further ...
New molecules and ways to effectively fight lymphomas are constantly being explored. One such approach is immuno-oncology which uses immunotherapies to treat cancer. Immuno-oncology refers to the use of the patients immune system to fight the patients cancer.
In this study we addressed the theoretical concern that CD20-targeted CAR T cells may be rendered ineffective by residual levels of rituximab. This question is relevant to future clinical trials enrolling patients with relapsed or refractory B-cell lymphomas treated recently with rituximab-containing salvage chemotherapy, who may have significant residual serum rituximab concentrations at the time of CAR T-cell infusion.. We defined the range of serum levels of rituximab that would likely be encountered in a CAR T-cell trial by examining a large cohort of patients treated at our center who had received rituximab-containing therapy within the previous 4 months. We found that the vast majority of patients had rituximab of 100 μg/mL or less, with a median value of less than 40 μg/mL. Within this range of rituximab concentrations, CD20-specific CAR T cells maintained significant activity both in vitro and in vivo despite partial blockade of CAR-binding sites, presumably due to a significant ...
Distinct genetic signatures can help distinguish responders from nonresponders of chimeric antigen receptor (CAR) T-cell treatment in patients diagnosed with chronic lymphocytic leukemia (CLL).
Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and ...
Open session proposals ought to be submitted in a single PDF or Word file to the secretarys office ( [email protected] ). The secretarys workplace will publish the proposals on the SHOT website. To hitch a proposed panel from the Open Periods checklist, contact the organizer for that panel, not the Program Committee. Open Session organizers will then assemble full panel sessions and submit them to SHOT by the top of the common name for papers on March 31, 2017. The Program Committee will assessment the ensuing absolutely fashioned session proposals, whether conventional or unconventional, for high quality and adherence to SHOT standards of gender, geographic, and institutional variety. Scientists at Juno Therapeutics reported on the American Society of Hematology (ASH) assembly that, in an ongoing Section 1 trial, its chimeric antigen receptor (CAR) T-cell therapy, JCAR015, put 24 of 27 adults with refractive acute lymphoblastic leukemia (ALL) into remission, with six patients remaining ...
The promise of cell and gene therapy is great, but not without its challenges. Complex processes, such as chimeric antigen receptor (CAR) T cell manufacturing, often require multiple steps that are performed across several devices. Unfortunately, hands-on manipulations like cell transfer between vessels and manual pipetting, always carry the the risk of contamination, human error, and cell loss.. The CliniMACS Prodigy® Platform automates cell processing from starting material to final cellular product in a single instrument. All major cell manufacturing steps are automated and standardized for increased reproducibility in a closed system to enable the production of GMP-compliant cell products.. A variety of cell manufacturing procedures are made possible by the CliniMACS Prodigy, including:. ...
The most common and potentially severe toxicity associated with CAR-modified T-cell therapy is CRS.25⇓-27,42 Early data from our group and others suggest that there may be a correlation between the development of CRS and the response to therapy; patients who do not develop CRS may be less likely to benefit from CAR-modified T cells, whereas those who develop CRS often respond to the therapy. Although there may be some correlation between developing CRS and efficacy, there does not appear to be a strong correlation between the degree of CRS and response to therapy. This is because of the confounding and strong impact of disease burden on the risk of severe CRS. Similar to other T-cell engaging therapies, including BiTE (bi-specific T-cell engaging) antibodies,49,50 we have found that the severity of CRS may correlate with tumor burden at time of infusion of the CAR-modified T cells.26. CRS is an inflammatory process related to exponential T-cell proliferation with resultant marked elevations in ...
This is a phase 1 dose escalation study designed to determine the maximum tolerated dose (MTD) of CAR modified T cells in patients with relapsed and refractory aggressive B-NHL. Three dose levels (5 x 106 19-28z T cells/kg, 1 x 107 19-28z T cells/kg, and 2 x 107 19-28z T cells/kg) are considered for the MTD ...
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Bring a little bit of Detroit to your local body shop. Home brew versions of X Y plotters are being created by hobbyists. Why noty scale up these low cost designs and have a robot auto painter follow an X Y plotter type track attached to the ceiling. The paint gun is attached to a telescoping pole attached to the X Y plotter. The plotter tracks could be raised and lowered to reduce the motion of the telescoping pole as it goes through its motions. Motion stabilizing technology, such as a used in video cameras, could also be deployed in order to steady the paint gun. At the paint gun end of the pole is a wrist or universal joint, The joint, telescoping pole, and X Y plotter controls the position of the paint gun. Software would be written to control the machine in painting specific car makes and models, the body shop would purchase the logarithm as required -- creating profit for the maker . Over time the device and programs would pay for themselves for the usual man versus robot reasons: less ...
The manufacturing process for Novartis chimeric antigen receptor T cell (CAR-T) cell therapy, Kymriah, requires the reprogramming of a patients T cells.. T cells, or T lymphocytes, are a subtype of white blood cell and play a key role in cell-mediated immunity.. Thermo Fishers CTS Dynabeads CD3/CD28 enables the ex vivo isolation, activation, and expansion of these cells, which are then genetically engineering to fight the cancer cells within an individual patient.. "The technology combines the use of anti-CD3 and anti-CD28 antibodies on the Dynabeads to provide both the primary and co-stimulatory signals that are required for activation and expansion of T cells​," Deb Barbara, senior director, therapeutic licensing and commercial supply at Thermo Fisher told Outsourcing-Pharma.com.. To ensure the technology met the quality standards set by Novartis, Thermo Fisher established a 21,000 sq. ft. aseptic manufacturing facility in Vilnius, Lithuania, which is dedicated to the GMP manufacturing of ...
The chimeric antigen receptor T (CAR-T) cell therapy is a new treatment for a variety of cancers. The idea is to take out the T-cells from the patient, and genetically engineer the cells to make them express a chimeric receptor (CAR) recognizing a specific tumor-associated antigen (TAAs). As a result, the CAR-expressing T cells, when reintroduced into the patients body, will target and eliminate the TAA-expressing tumor cells.. Despite the early excitement, the actual path to a clinical success is not an easy one. Both Junos and Kite Pharmas clinical trials ended up with unexpected and unexplained deaths caused by cerebral edema, which cast a dark shadow over the entire field.. The long-awaited breakthrough finally came this year. Kymriah, Novartiss CAR-T therapy, was approved by FDA this August for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse. This success marks a milestone in the development of targeted cell ...
In the pivotal Novartis trial, 83 percent of patients achieved remission with a disease that has historically poor outcomes.. The therapy was evaluated in clinical testing involving 63 children and young adults with relapsed or refractory B-cell ALL. The patients T-cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a specific protein (a chimeric antigen receptor or CAR) that directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface. According to Childrens of Alabama, more than 190 children in Alabama are diagnosed with various forms of cancer each year, including ALL.. This first use of CAR-T therapy is aimed at patients desperately ill with acute lymphoblastic leukaemia, which strikes more than 3,000 children and young adults in the United States each year.. Novartis has not yet announced the cost for the therapy, but British health authorities have said a price of ...
JUNO data by YCharts.. What: Juno Therapeutics (NASDAQ:JUNO), a clinical-stage cancer immunotherapy company, saw its shares lose more than 20% of their value in December, according to data provided by S&P Capital IQ. The stocks decline was apparently driven by the companys array of clinical updates provided at the American Society of Hematology meeting last month. So what: Although Juno reported that its chimeric antigen receptor (CAR) T cell product candidates, JCAR015 and JCAR014, showed encouraging clinical responses in patients with relapsed or refractory acute lymphoblastic leukemia, a fair number patients in some trials experienced serious side effects such as cytokine release syndrome and/or neurotoxicity. Such adverse effects are a well-known problem associated with CAR T-cell therapies in general. Thats why some of Junos main competitors like Bellicum Pharmaceuticals (NASDAQ:BLCM) are working diligently on so-called "suicide switches" that can reduce the risks of these potent ...
Michel Sadelain, MD, PhD, Director, Center for Cell Engineering and Gene Transfer and Gene Expression Laboratory, Stephen and Barbara Friedman Chair, Memorial Sloan Kettering Cancer Center (MSK), discusses chimeric antigen receptor (CAR) t-cell therapies.
One of the most important questions that immuno-oncologists will tackle in the coming years is figuring out where chimeric antigen receptor (CAR) T-cell therapy will fit into the larger picture. Academic centers across the country have been using this technology to successfully treat patients, but adapting this complicated system to a community setting introduces a… Read More…. ...
Considerable progress has been made in cancer therapeutics recently with targeted strategies that are efficacious and less toxic. Immunotherapy and chimeric antigen receptor (CAR) T-cells are...
I am having problems with my FIRESTORM 36x cd rom, it will not read CDs anymore. I upgraded to win98 about 2 weeks ago, since then the performence of my CD ROM has degraded to the point that it will not even read the route dir. It worked fine under win95 osr2, is this coinsidence or is it a win98 problem. Also does anyone know who makes the FIRESTORM 36x CD ROM.
A variety of cell surface markers have been proposed for different regulatory B cell subsets (21, 22). The generalized ex vivo phenotype of B10 cells from untreated mice is IgMhighIgDlowCD1dhighCD5+CD19highCD23lowB220high, with ,10% coexpressing IgG or IgA (13, 15, 35, 38). Thereby, spleen B10 cells share surface markers with multiple phenotypically defined B cell subsets, including transitional, marginal zone, marginal zone precursor, memory, and B1 B cells (6, 11, 13-15, 38, 41, 43, 44). Spleen B10 cells are enriched within the CD1dhighCD5+CD19high subpopulation (Fig. 2), where 15-20% are B10 cells, and up to 50% are B10+B10pro cells (6, 13, 15, 29). Small numbers of B10 cells are also found within other spleen B cell fractions. The phenotype of B10pro cells after culture reflects their in vitro activation more than their subset of origin. For example, most mouse and human B cells upregulate CD5 expression following CD40 stimulation in vitro (31, 32). Spleen IL-10+ B cells are also enriched ...
Cancer Lett. 2012 Mar;316(1):1-5. doi: 10.1016/j.canlet.2011.10.027. Epub 2011 Oct 29. Research Support, Non-U.S. Govt; Review
06 Jan 2017. Promising results from the phase 1 portion of the ZUMA-1 study, which uses chimeric antigen receptor (CAR) modified T cells to treat b-cell lymphoma patients, were published in the January issue of Molecular Therapy, the official journal of the American Society of Gene and Cell Therapy.. These results were first discussed at ASH 2016 by co-author Dr Sattva Neelapu.. Axicabtagene ciloleucel (KTE-C19), developed by Kite Pharma, is an autologous chimeric antigen receptor (CAR) T-cell therapy.. In CAR-T therapy using axicabtagene ciloleucel (KTE-C19), T cells are isolated from a patients blood and engineered in Kite Pharmas central manufacturing facility to target the CD19 protein that is found on lymphoma cells. The re-targeted T cells are then infused back into the same patient. Axicabtagene ciloleucel (KTE-C19) T cells are able to recognise cancerous lymphoma cells that express CD19 and target them for destruction.. The goal of the phase 1 portion of the ZUMA-1 study was to ...
Promising data from trials investigating T/NK-cells modified to express CARs against tumour antigens have generated extensive interest from clinicians, researchers and pharmaceutical companies, leading to broaden the applications of CARs beyond cancer through other pathologies, as autoimmune diseases or allograft rejection [13,14]. Autoimmunity can be broadly separated in two processes: via self-reactive antibodies or "autoantibodies" (produced by plasma cells from the B lymphocyte lineage), and/or via self-reactive T-lymphocytes. This may occur during the processes of selection of those cells during their development (central tolerance), in which negative selection to self-antigens fails, or due to changes in target tissues (break of peripheral tolerance). Between these peripheral autoimmune mechanisms, there are the autorreactivitiy against the so-called "sequestered antigens" (self-antigens present in isolated areas of the organism that are not exposed in normal conditions), that become ...
The continuously growing natural killer (NK) cell line NK-92 is highly cytotoxic against malignant cells of various origin without affecting normal human cells. Based on this selectivity, the potential of NK-92 cells for adoptive therapy is currently being investigated in phase I clinical studies. To further enhance the antitumoral activity of NK-92 cells and expand the range of tumor entities suitable for NK-92-based therapies, here by transduction with retroviral vectors we have generated genetically modified NK-92 cells expressing chimeric antigen receptors specific either for the tumor-associated ErbB2 (HER2/neu) antigen or the human Epithelial Cell Adhesion Molecule (Ep-CAM). Both antigens are overexpressed by many tumors of epithelial origin. The chimeric antigen receptors consist of either the ErbB2 specific scFv(FRP5) antibody fragment or the Ep-CAM specific scFv(MOC31), a flexible hinge region derived from CD8, and transmembrane and intracellular regions of the CD3 zeta chain. ...
The use of chimeric antigen receptor (CAR)Cmodified T cells as a therapy for hematologic malignancies and solid tumors is becoming even more widespread. modified by giving epigenetic modulators that upregulated focus on manifestation and improved CAR T-cell strength. Intro Capital t cells altered to communicate tumor-directed chimeric antigen receptors (Vehicles) possess demonstrated medical effectiveness in dealing with both hematological malignancies and solid tumors.1,2,3,4,5,6 It is likely, nevertheless, that the the majority of effective make use of of CAR-modified T cells will need extra design to allow them to overcome growth defense get away systems. One of the most essential of these get away strategies is usually focus on antigen modulation under picky pressure.7 This trend has been reported as a trigger of failing in both preclinical and medical research using adoptively moved T cells with sole antigen 1431697-90-3 manufacture specificity to deal with heterogeneous tumors,7,8,9 and ...
Key clinical point: A chimeric antigen receptor (CAR) T-cell cocktail targeting both CD19 and CD22 could improve outcomes for patients with refractory or relapsed B-cell malignancies.Major finding: Among patients with B-cell acute lymphoblastic leukemia, minimal residual disease-negative complete response rate was 96%.Study details: An open-label, single-arm pilot study involving 89 patients with refractory/relapsed B cell malignancies.
Advances in genetic engineering have made it possible to reprogram individual immune cells to express receptors that recognise markers on tumour cell surfaces. The process of re-engineering T cell lymphocytes to express Chimeric Antigen Receptors (CARs), and then re-infusing the CAR-modified T cells into patients to treat various cancers is referred to as CAR T cell therapy. This therapy is being explored in clinical trials - most prominently for B Cell Acute Lymphoblastic Leukaemia (B-ALL), a common B cell malignancy, for which CAR T cell therapy has led to remission in up to 90% of patients. Despite this extraordinary response rate, however, potentially fatal inflammatory side effects occur in up to 10% of patients who have positive responses. Further, approximately 50% of patients who initially respond to the therapy relapse. Significant improvement is thus necessary before the therapy can be made widely available for use in the clinic. To inform future development, we develop a mathematical ...
Switzerland-based Novartis (NVS) announced findings from a pilot study of CTL119 that had dazzling results.. CTL119 is a CAR-T cell therapy, where T cells that express chimeric antigen receptors (CAR) are engineered to target any cancer antigen desired. In the early study, nine patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who had been on Imbruvica (ibrutinib) for at least six months, but were not in complete remission, had CTL119 added to their therapy regiment. In three months, eight of the nine patients showed no signs of CLL in their bone marrow. One of the patients had a partial response. There were a total of 10 patients in the study, but one did not produce data that could be evaluated. "The data from this pilot study support the potential for CTL119, when combined with the kinase inhibitor ibrutinib, to induce clinically-significant responses in high-risk CLL patients who were unlikely to achieve a complete remission on ibrutinib alone," said James Bradner, ...
Chronic Lymphocytic Leukemia (CLL) - anti-CD19 Chimeric Antigen Receptor (CAR)-T cell therapy with defined T-cell subsets for ibrutinib-refractory patients: presentation at the international workshop on CLL (iwCLL) 2017
BACKGROUND. Chimeric antigen receptor (CAR) T cells can induce remission in highly refractory leukemia and lymphoma subjects, yet the parameters for achieving sustained relapse-free survival are not fully delineated. METHODS. We analyzed 43 pediatric and young adult subjects participating in a phase I trial of defined composition CD19 CAR T cells (ClinicalTrials.gov, NCT02028455). CAR T cell phenotype, function, and expansion, as well as starting material T cell repertoire, were analyzed in relationship to therapeutic outcome (defined as achieving complete remission within 63 days) and duration of leukemia-free survival and B cell aplasia. RESULTS. These analyses reveal that initial therapeutic failures (n = 5) were associated with attenuated CAR T cell expansion and/or rapid attrition of functional CAR effector cells following adoptive transfer. The CAR T products were similar in phenotype and function when compared with products resulting in sustained remissions. However, the initial apheresed ...
A grant from The Leukemia & Lymphoma Society will help fund clinical research led by UNC Linebergers Barbara Savoldo, MD, PhD, into an investigational chimeric antigen receptor (CAR) T-cell treatment for acute lymphoblastic leukemia that would include a built-in safety switch.
We initiated a first-in-human pilot study of intravenous delivery of a single dose of autologous T cells re-directed to the EGFR variant III (EGFRvIII) mutation by means of a lentiviral vector encoding a chimeric antigen receptor (CAR). We report our findings on the first ten recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CART- EGFRvIII cells is feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up.
Targeted and personalized therapeutics are likely to transform the existing precision medicine landscape. With recent landmark regulatory approval, CAR T therapy has the potential to emerge as the industry standard for cancer management in the future and potentially replace existing treatment techniques. Bispecific and multi-specific antibody platforms are likely to emerge as the preferred alternatives for existing monotherapy strategies as they offer increased therapeutic efficacy, while reducing off-target effects. This global research service provides comprehensive insights across key technologies, research trends, funding IP outlook, clinical trials and industry innovations that are likely to transform the landscape of chimeric antigen receptor (CAR) T cell and bispecific/multi-specific T cell engaging immunotherapies.
Treatment with chimeric antigen receptor (CAR) T cells has shown promise against hematologic cancers, but it hasnt worked well against solid tumors. However, a study published this month shows that injecting the T cells into the area around the tumor improves the effectiveness of the therapy in mice.. CAR T-cell treatment involves removing some of a patients T cells and genetically modifying them to carry a T-cell receptor that recognizes a specific antigen. After the reprogrammed T cells are returned to the patients bloodstream, they destroy cancer cells they encounter that carry their target antigen.. Based on other research, one reason that the therapy hasnt performed as well against solid tumors as against hematologic cancers might be that few of the CAR T cells are reaching the tumors, notes Prasad Adusumilli, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York, NY. Consequently, a team led by Adusumilli and his MSKCC colleague Michel Sadelain, MD, PhD, decided to try ...
Rye Brook, N.Y. (August 30, 2017) - Today heralds a new era in cancer treatment with the U.S. Food and Drug Administration (FDA) approval of a new, cutting-edge gene therapy that reprograms a patients immune system to find and kill cancer cells. This highly personalized therapy known as Kymriah (previously CTL019 or tisagenlecleucel-T) signifies the promise of CAR (chimeric antigen receptor) T-cell immunotherapy, an approach that The Leukemia & Lymphoma Society (LLS) recognized early on held great promise for blood cancer patients.
This story first appeared on the Mayo Clinic News Network. Mayo Clinic announced recently that its Rochester campus is one of 16 cancer centers nationally selected to provide chimeric antigen receptor T-cell therapy (CAR T-cell therapy) for adults with B-cell non-Hodgkin lymphoma who have not responded to, or have relapsed, after two or more lines of treatment. The therapy, […]. ...
It doesnt have any gene-editing medicines in human clinical trials yet, but plans to begin trials next year. The companys first gene-editing target is a rare inherited eye disorder called LCA10, and it says its on track to file for approval from the U.S. Food and Drug Administration to begin enrolling patients in phase 1 studies by the middle of 2018.. Editas Medicine is also making preclinical-stage progress in using gene editing to create next-generation chimeric antigen receptor T-cell therapy (CAR-T). The companys CAR-T research is being done under an agreement with Juno Therapeutics (NASDAQ:JUNO), a leader in T-cell reengineering.. According to Editas Medicine, it has achieved milestones in creating T-cells or T-cell receptors (TCRs) that can overcome the tumor microenvironment and boost T-cell persistence. These advances are important because they could lead to more effective and safe CAR-T and TCR therapies.. Editas Medicine also said it bolstered its patent portfolio by adding a ...
We arrived home in Woods Cross Friday night without signing the CART-19 (chimeric antigen receptor T-cell) protocol. Right before we flew east to Pennsylvania a man had died from the treatment so the trial was on hold. We could feel the tension from the head research coordinator as we sat down in apheresis for Marshalls vein consultation. The room was freezing and the nurses checked and double checked Marshalls arms to determine if they would be able to collect what they needed. The first nurse needed a second opinion. We were becoming discouraged because the last time they tried to collect his blood in Salt Lake they had to poke him six times. This is not uncommon for patients who have been through so much. Marshall has had 2 stem cell transplants and hes had a central line twice, but each time he has relapsed his central line had already been removed months prior to the relapse, so he has been poked and prodded up the wazoo. And that was just for small blood collections, not a 3 hour T-cell ...
Copyright 2013 by the Massachusetts General Hospital. Some sections copyright 2008-2009 by The President and Fellows of Harvard College.. ...
Safety and feasibility of chimeric antigen receptor T cell therapy after allogeneic hematopoietic cell transplantation in relapsed/ refractory B cell non-Hodgkin lymphoma Letter ...
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.
Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported
B cells play critical roles in the pathogenesis of lupus. To examine the influence of B cells on disease pathogenesis in a murine lupus model, New Zealand Black and New Zealand White F1 hybrid (NZB/W) mice were generated that were deficient for CD19 (CD19−/− NZB/W mice), a B cell-specific cell surface molecule that is essential for optimal B cell signal transduction. The emergence of anti-nuclear Abs was significantly delayed in CD19−/− NZB/W mice compared with wild type NZB/W mice. However, the pathologic manifestations of nephritis appeared significantly earlier, and survival was significantly reduced in CD19−/− NZB/W mice compared with wild type mice. These results demonstrate both disease-promoting and protective roles for B cells in lupus pathogenesis. Recent studies have identified a potent regulatory B cell subset (B10 cells) within the rare CD1dhiCD5+ B cell subset of the spleen that regulates acute inflammation and autoimmunity through the production of IL-10. In wild type ...

Therapeutic Targeting of Lewisy and Lewisb with a Novel Monoclonal Antibody 692/29Therapeutic Targeting of Lewisy and Lewisb with a Novel Monoclonal Antibody 692/29

Rejection of Experimental Hodgkins Lymphoma by T-Cells Engineered with a CD19 Chimeric Antigen Receptor. Swanson, Anna; Cheadle ... 692/29 has a more restricted normal tissue distribution and a higher antigen threshold for killing which should reduce its ... T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T ...
more infohttp://connection.ebscohost.com/c/articles/87623541/therapeutic-targeting-lewisy-lewisb-novel-monoclonal-antibody-692-29

Recombinant Human B-lymphocyte antigen CD19(CD19),partial - CusabioRecombinant Human B-lymphocyte antigen CD19(CD19),partial - Cusabio

CD19),partial. It is produced in in vitro E.coli expression system. High purity. Good price. ... B-lymphocyte antigen CD19; B-lymphocyte surface antigen B4; B4; CD19; CD19 antigen; CD19 molecule; Cd19 protein; CD19_HUMAN; ... CD19 Proteins. *Recombinant Human B-lymphocyte antigen CD19(CD19),partial ( in vitro E.coli expression system-CSB-CF004888HU ) ... ELISA Kit deficiency due to defect in CD19; deficiency due to defect in CD19; included; AW495831; B lymphocyte antigen CD19; B ...
more infohttps://www.cusabio.com/Transmembrane-Protein/Recombinant-Human-B-lymphocyte-antigen-CD19CD19partial-12556579.html

In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the CD19...In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the CD19...

Genetically Targeted to the CD19 Antigen in B-cell Malignancies. The safety and scientific validity of this study is the ... genetically modified to target the B-cell antigen CD19 when administered to patients with CD19+. ... Genetically Targeted to the CD19 Antigen in B-cell Malignancies. ... To assess the effects of the adoptively transferred CD19 ... To quantitate the number of chimeric antigen receptor (CAR) positive T-cells and donor EBV-CTL in the blood at defined ...
more infohttps://clinicaltrials.gov/ct2/show/NCT01430390

In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the CD19...In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the CD19...

Genetically Targeted to the CD19 Antigen in B-cell Malignancies. This study is currently recruiting participants. See Contacts ...
more infohttps://clinicaltrials.gov/ct2/show/results/NCT01430390

Development and Characterization of Three Recombinant Single Chain Antibody Fragments (scFvs) Directed against the CD19 Antigen...Development and Characterization of Three Recombinant Single Chain Antibody Fragments (scFvs) Directed against the CD19 Antigen...

... were properly refolded and bound CD19 antigen in FACS competition assays. These anti-CD19 scFv should be useful in the further ... Antibodies that recognize the CD19 antigen found on normal and malignant B cells, but not on stem cells, have been used to ... Directed against the CD19 Antigen. Bruce E. Bejcek, Duo Wang, Erica Berven, Christopher A. Pennell, Stephen C. Peiper, Sibrand ... Development and Characterization of Three Recombinant Single Chain Antibody Fragments (scFvs) Directed against the CD19 Antigen ...
more infohttp://cancerres.aacrjournals.org/content/55/11/2346.long

Antigens, CD19 | Colorado PROFILESAntigens, CD19 | Colorado PROFILES

CD19" by people in this website by year, and whether "Antigens, CD19" was a major or minor topic of these publications. ... "Antigens, CD19" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... Zhang W, Jordan KR, Schulte B, Purev E. Characterization of clinical grade CD19 chimeric antigen receptor T cells produced ... Human CD19-Targeted Mouse T Cells Induce B Cell Aplasia and Toxicity in Human CD19 Transgenic Mice. Mol Ther. 2018 06 06; 26(6 ...
more infohttps://profiles.ucdenver.edu/display/218800

Construction and Preclinical Evaluation of an Anti-CD19 Chimeric Antigen ReceptorConstruction and Preclinical Evaluation of an Anti-CD19 Chimeric Antigen Receptor

We constructed and compared 2 CARs that contained a single chain variable region moiety that recognized CD19. One CAR contained ... T cells can be engineered to express the genes of chimeric antigen receptors (CARs) that recognize tumor-associated antigens. ... Anti-CD19-CAR-transduced CD8+ and CD4+ T cells produced interferon-γ and interleukin-2 specifically in response to CD19+ target ... T cells can be engineered to express the genes of chimeric antigen receptors (CARs) that recognize tumor-associated antigens. ...
more infohttps://insights.ovid.com/crossref?an=00002371-200909000-00002

Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells associate with clinical outcomes in NHL | Blood JournalPreinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells associate with clinical outcomes in NHL | Blood Journal

Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells associate with clinical outcomes in NHL. John Rossi, ... Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells associate with clinical outcomes in NHL. Blood, (), ... Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells associate with clinical outcomes in NHL ... Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells associate with clinical outcomes in NHL ...
more infohttp://www.bloodjournal.org/content/early/2018/06/12/blood-2018-01-828343?sso-checked=true

CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia | Blood JournalCD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia | Blood Journal

Two modes of disease recurrence have been seen: CD19 positive and CD19 negative. Relapse of ALL that retains surface CD19 ... CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Shannon L. Maude, David T. Teachey, ... CD19: an ideal target?. Ideally, an antigen targeted by CAR-modified T cells would be tumor specific. Beyond that, an ideal ... Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol 2013;10(5):267-276. ...
more infohttp://www.bloodjournal.org/content/125/26/4017?sso-checked=true

Kite Pharma Announces Patients With Aggressive Non-Hodgkins Lymphoma Experience Positive Results After Receiving Anti-CD19...Kite Pharma Announces Patients With Aggressive Non-Hodgkin's Lymphoma Experience Positive Results After Receiving Anti-CD19...

... a cohort of patients demonstrating the potential to treat aggressive non-Hodgkins lymphoma with an anti-CD19 chimeric antigen ... and Indolent B-cell Malignancies Can Be Effectively Treated with Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen ... Kites most advanced product candidate, KTE-C19, is an anti-CD19 CAR T cell therapy that involves genetically modifying a ... As seen in other studies, infusion of anti-CD19 CAR T cells was associated with significant, acute toxicities, including fever ...
more infohttp://www.gilead.com/news/press-releases/2014/8/kite-pharma-announces-patients-with-aggressive-nonhodgkins-lymphoma-experience-positive-results-after-receiving-anticd19-chimeric-antigen-receptor-car-t-cells-at-the-national-cancer-institute-nci

CD19-redirected chimeric antigen receptor (CD19 CAR) T cell in the clinical treatment of human non-Hodgkinâ  s lymphoma and...CD19-redirected chimeric antigen receptor (CD19 CAR) T cell in the clinical treatment of human non-Hodgkinâ s lymphoma and...

CD19-redirected chimeric antigen receptor (CD19 CAR) T cell in the clinical treatment of human non-Hodgkins lymphoma and acute ... CD19 CAR T cell-redirected immunotherapy is an attractive option for patients with various CD19+ leukemias (e.g., ALL) and ... In fact, anti-CD19 CAR T-cell therapy has shown remarkable clinical efficacy in the treatment of these patients. Its ... Recently, a new form of immunotherapy using genetically engineered chimeric antigen receptor (CAR) T-cells has been developed. ...
more infohttps://www.pulsus.com/abstract/cd19redirected-chimeric-antigen-receptor-cd19-car-t-cell-in-the-clinical-treatment-of-human-nonhodgkins-lymphoma-and-acu-5173.html

Evaluation of Ricin A Chain-containing Immunotoxins Directed against CD19 and CD22 Antigens on Normal and Malignant Human B...Evaluation of Ricin A Chain-containing Immunotoxins Directed against CD19 and CD22 Antigens on Normal and Malignant Human B...

In most cases, their sensitivity correlated with the levels of CD19 and CD22 antigens expressed. Neither HD6 nor HD37 IT-As ... Ricin A chain-containing immunotoxins (IT-As) specific for the human B-cell antigens, CD22 and CD19, were constructed using the ... Evaluation of Ricin A Chain-containing Immunotoxins Directed against CD19 and CD22 Antigens on Normal and Malignant Human B- ... Evaluation of Ricin A Chain-containing Immunotoxins Directed against CD19 and CD22 Antigens on Normal and Malignant Human B- ...
more infohttp://cancerres.aacrjournals.org/content/48/9/2610

Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified...Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified...

CD19-specific chimeric antigen receptor (CAR)-modified T cells have antitumor activity in B cell malignancies, but factors that ... Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified ... Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified ... Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified ...
more infohttps://stm.sciencemag.org/content/8/355/355ra116.abstract

CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22...CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22...

CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22- ... CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22- ... CD19 immune escape has been observed by several groups following CD19-CAR therapy for B-ALL. Investigation of this phenomenon ... This trial will test whether simultaneous targeting of CD19 and CD22 using a novel bivalent CD19/22-CAR is safe and feasible. ...
more infohttps://www.centerwatch.com/clinical-trials/listings/194878/acute-lymphoid-leukemia-cd19cd22-chimeric-antigen-receptor/?radius=50

Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified...Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified...

CD19-specific chimeric antigen receptor (CAR)-modified T cells have antitumor activity in B cell malignancies, but factors that ... Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified ... Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified ... Immunotherapy of non-Hodgkins lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified ...
more infohttp://stm.sciencemag.org/content/8/355/355ra116

Pleural cavity cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy, Medicine | 10.1097...Pleural cavity cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy, Medicine | 10.1097...

"Pleural cavity cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy, Medicine" on ... T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 ... Pleural cavity cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy. Ding, Lijuan; Hu, ... Pleural cavity cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T... Ding, Lijuan; Hu, Yongxian; ...
more infohttps://www.deepdyve.com/lp/wolters_kluwer/pleural-cavity-cytokine-release-syndrome-in-cd19-directed-chimeric-fJqlafcZ6W

Toward targeting B cell cancers with CD4+ CTLs: identification of a CD19-encoded minor histocompatibility antigen using a novel...Toward targeting B cell cancers with CD4+ CTLs: identification of a CD19-encoded minor histocompatibility antigen using a novel...

Toward targeting B cell cancers with CD4+ CTLs: identification of a CD19-encoded minor histocompatibility antigen using a novel ... Toward targeting B cell cancers with CD4+ CTLs: identification of a CD19-encoded minor histocompatibility antigen using a novel ...
more infohttp://jem.rupress.org/content/early/2008/11/10/jem.20080713

The efficacy and safety of anti-CD19/CD20 chimeric antigen receptor- T cells immunotherapy in relapsed or refractory B-cell...The efficacy and safety of anti-CD19/CD20 chimeric antigen receptor- T cells immunotherapy in relapsed or refractory B-cell...

Chimeric antigen receptor T (CAR T) cells immunotherapy is rapidly developed in treating cancers, especially relapsed or ... Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: ... Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in ... T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 ...
more infohttps://bmccancer.biomedcentral.com/articles/10.1186/s12885-018-4817-4

Kite Pharma Announces Patients With Aggressive Non-Hodgkins Lymphoma Experience Positive Results After Receiving Anti-CD19...Kite Pharma Announces Patients With Aggressive Non-Hodgkin's Lymphoma Experience Positive Results After Receiving Anti-CD19...

... a cohort of patients demonstrating the potential to treat aggressive non-Hodgkins lymphoma with an anti-CD19 chimeric antigen ... and Indolent B-cell Malignancies Can Be Effectively Treated with Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen ... Kites most advanced product candidate, KTE-C19, is an anti-CD19 CAR T cell therapy that involves genetically modifying a ... As seen in other studies, infusion of anti-CD19 CAR T cells was associated with significant, acute toxicities, including fever ...
more infohttp://ir.kitepharma.com/releasedetail.cfm?ReleaseID=867609

The efficacy of anti-CD19 chimeric antigen receptor T cells for B-cell malignancies.  - PubMed - NCBIThe efficacy of anti-CD19 chimeric antigen receptor T cells for B-cell malignancies. - PubMed - NCBI

The efficacy of anti-CD19 chimeric antigen receptor T cells for B-cell malignancies.. Cao JX1, Gao WJ1, You J1, Wu LH1, Liu JL1 ... Immunotherapy with chimeric antigen receptor T (CAR-T) cells has proved remarkably effective in recently published clinical ... In conclusion, this meta-analysis showed a high clinical RR of CD19-CAR-T cell-based immunotherapy in patients with refractory ... The overall pooled RR of CD19-CAR-T cells was 72% (95% confidence interval: 62-77%). The various clinical parameters were ...
more infohttps://phgkb.cdc.gov/PHGKB/phgHome.action?action=forward&dbsource=huge&id=175680

Predominant cerebral cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy | Journal of...Predominant cerebral cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy | Journal of...

T cells targeting CD19 (CART19) have shown therapeutical activities in CD19+ malignancies. However, the etiological nature of ... T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 ... Chimeric antigen receptor-modified (CAR) T cells targeting CD19 (CART19) have shown therapeutical activities in CD19+ ... Chimeric antigen receptor-modified (CAR) T cells targeting CD19 (CART19) have shown therapeutical activities in refractory/ ...
more infohttps://jhoonline.biomedcentral.com/articles/10.1186/s13045-016-0299-5

Blinatumomab - DrugBankBlinatumomab - DrugBank

CD19. Uniprot ID. P15391. Uniprot Name. B-lymphocyte antigen CD19. Molecular Weight. 61127.985 Da. ... Assembles with the antigen receptor of B-lymphocytes in order to decrease the threshold for antigen receptor-dependent ... Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that binds to CD19 expressed on the surface of cells of B-lineage ... B Acute Lymphoblastic Leukemia / B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / CD19-Positive Neoplastic ...
more infohttps://www.drugbank.ca/drugs/DB09052

KEGG BRITE: KEGG Orthology (KO) - Camelus ferus (Wild Bactrian camel)KEGG BRITE: KEGG Orthology (KO) - Camelus ferus (Wild Bactrian camel)

K06465 CD19; B-lymphocyte antigen CD19 K12230 PIK3AP1; phosphoinositide 3-kinase adapter protein 1 K05438 GH; growth hormone ... 102506736 CD19; CD19 molecule 102505471 PIK3AP1; phosphoinositide-3-kinase adaptor protein 1 102518081 GH1; growth hormone 1 ... CD36 antigen K06259 CD36; CD36 antigen K18052 PRKCQ; novel protein kinase C theta type [EC:2.7.11.13] K06068 PRKCD; novel ... CD36 antigen K06259 CD36; CD36 antigen K05459 IGF1; insulin-like growth factor 1 K05087 IGF1R; insulin-like growth factor 1 ...
more infohttp://www.genome.jp/kegg-bin/get_htext?cfr00001+102511249

KEGG BRITE: KEGG Orthology (KO) - Equus caballus (horse)KEGG BRITE: KEGG Orthology (KO) - Equus caballus (horse)

K06465 CD19; B-lymphocyte antigen CD19 K12230 PIK3AP1; phosphoinositide 3-kinase adapter protein 1 K05438 GH; growth hormone ... 100147468 CD19; CD19 molecule 100070796 PIK3AP1; phosphoinositide-3-kinase adaptor protein 1 100034180 GH1; growth hormone 1 ... 100060245 MGEA5; meningioma expressed antigen 5 (hyaluronidase) 100056148 OGT; O-linked N-acetylglucosamine (GlcNAc) ... CD36 antigen K18052 PRKCQ; novel protein kinase C theta type [EC:2.7.11.13] K06068 PRKCD; novel protein kinase C delta type [EC ...
more infohttp://www.genome.jp/kegg-bin/get_htext?ecb00001+100054723
  • Anti-CD19 exhibits an overall immunoreactivity pattern similar to those of the antibodies against CD20 and CD22. (biotium.com)
  • Unfortunately, some clinical studies have shown that there is a loss of CD19 or CD20 expression in various cases of lymphomas and leukemias, particularly after treatment with an agent that targets CD19 (e.g., anti-CD19 CAR-T). However, studies have shown that expression of one protein is retained when the other is lost. (cancer.gov)
  • This suggests that a therapeutic with the ability to simultaneously target both CD19 and CD20 could represent a solution to the drawbacks of current therapies. (cancer.gov)
  • Researchers at the National Cancer Institute (NCI) have developed the current invention which is an expression construct for a CAR that targets both CD19 and CD20. (cancer.gov)
  • The result is a more efficient and simultaneous targeting of both CD19 and CD20 by the same T cell. (cancer.gov)
  • Ricin A chain-containing immunotoxins (IT-As) specific for the human B-cell antigens, CD22 and CD19, were constructed using the monoclonal antibodies, HD6 and HD37, respectively. (aacrjournals.org)
  • In most cases, their sensitivity correlated with the levels of CD19 and CD22 antigens expressed. (aacrjournals.org)
  • However, HD6 IT-As are more potent, reduce protein synthesis more completely, and hence appear to be the ITs of choice for treating tumors expressing the CD22 antigen. (aacrjournals.org)
  • 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)
  • Sequential therapy using CD22-CARs to treat CD19 dim/lo escape is associated with rapid development of resistance due to CD22 downregulation. (centerwatch.com)
  • This trial will test whether simultaneous targeting of CD19 and CD22 using a novel bivalent CD19/22-CAR is safe and feasible. (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)
  • These anti-CD19 scFv should be useful in the further development of diagnostic and therapeutic molecules. (aacrjournals.org)
  • CD19 is a transmembrane glycoprotein that contains two extracellular immunoglobulin-like domains. (biotium.com)
  • Antigens, CD19" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (ucdenver.edu)