Substances that are recognized by the immune system and induce an immune reaction.
Substances elaborated by bacteria that have antigenic activity.
Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers.
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.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
Substances elaborated by viruses that have antigenic activity.
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.
Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.
Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.
Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
Substances of fungal origin that have antigenic activity.
Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.
The major group of transplantation antigens in the mouse.
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.
Antibodies produced by a single clone of cells.
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.
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.
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.
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.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
A 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.
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.
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.
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.
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.
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.
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.
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)
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.
Sites on an antigen that interact with specific antibodies.
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.
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.
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.
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
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.
Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.
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.
Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.
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.
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.
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.
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.
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by 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.
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.
Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific 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.
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.
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.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
Established cell cultures that have the potential to propagate indefinitely.
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).
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.
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.
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.
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.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
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.
An encapsulated lymphatic organ through which venous blood filters.
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.
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.
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).
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.
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).
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A 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.
Glycoproteins found on the membrane or surface of cells.
Antigens associated with specific proteins of the human adult T-cell immunodeficiency virus (HIV); also called HTLV-III-associated and lymphadenopathy-associated virus (LAV) antigens.
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.
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.
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.
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.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.
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.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Antigens stimulating the formation of, or combining with heterophile antibodies. They are cross-reacting antigens found in phylogenetically unrelated species.
The hepatitis B antigen within the core of the Dane particle, the infectious hepatitis virion.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
A costimulatory receptor that is specific for INDUCIBLE T-CELL CO-STIMULATOR LIGAND. The receptor is associated with a diverse array of immunologically-related effects including the increased synthesis of INTERLEUKIN 10 in REGULATORY T-LYMPHOCYTES and the induction of PERIPHERAL TOLERANCE.
Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.
A 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.
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.
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.
A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*07 allele family.
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.
Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens.
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.
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.
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.
The sum of the weight of all the atoms in a molecule.
The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.
Immunoglobulins produced in response to VIRAL ANTIGENS.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
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.
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.
An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.
A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
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.
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.
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.
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.
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.
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.
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.
Proteins prepared by recombinant DNA technology.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
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.
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.
Immunoglobulins produced in a response to PROTOZOAN ANTIGENS.
Sialylated Lewis blood group carbohydrate antigen found in many adenocarcinomas of the digestive tract, especially pancreatic tumors.
Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Sensitive tests to measure certain antigens, antibodies, or viruses, using their ability to agglutinate certain erythrocytes. (From Stedman, 26th ed)
A melanosome-associated protein that plays a role in the maturation of the MELANOSOME.
Diagnostic procedures involving immunoglobulin reactions.
A group of dominantly and independently inherited antigens associated with the ABO blood factors. They are glycolipids present in plasma and secretions that may adhere to the erythrocytes. The phenotype Le(b) is the result of the interaction of the Le gene Le(a) with the genes for the ABO blood groups.
The grafting of skin in humans or animals from one site to another to replace a lost portion of the body surface skin.
Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.
A CELL CYCLE and tumor growth marker which can be readily detected using IMMUNOCYTOCHEMISTRY methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells.
Immunoglobulins produced in a response to HELMINTH ANTIGENS.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
Antigens which may directly stimulate B lymphocytes without the cooperation of T lymphocytes.
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.
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)
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.
Elements of limited time intervals, contributing to particular results or situations.
A closely related group of antigens found in the plasma only during the infective phase of hepatitis B or in virulent chronic hepatitis B, probably indicating active virus replication; there are three subtypes which may exist in a complex with immunoglobulins G.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
An increased reactivity to specific antigens mediated not by antibodies but by cells.
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.
Carbohydrate antigen most commonly seen in tumors of the ovary and occasionally seen in breast, kidney, and gastrointestinal tract tumors and normal tissue. CA 125 is clearly tumor-associated but not tumor-specific.
A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.
Immunologically detectable substances found in the CELL NUCLEUS.
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.
Allelic alloantigens often responsible for weak graft rejection in cases when (major) histocompatibility has been established by standard tests. In the mouse they are coded by more than 500 genes at up to 30 minor histocompatibility loci. The most well-known minor histocompatibility antigen in mammals is the H-Y antigen.
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.
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.
A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*27 allele family.
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)
A technique using antibodies for identifying or quantifying a substance. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance.
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)
Antigens produced by various strains of HEPATITIS D VIRUS.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the C locus on chromosome 6. They have significantly lower immunogenicity than the HLA-A and -B determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondylarthritis, psoriasis, multiple myeloma).
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.
A major histocompatibily complex class I-like protein that plays a unique role in the presentation of lipid ANTIGENS to NATURAL KILLER T-CELLS.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*01 allele family.
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.
Polysaccharides found in bacteria and in capsules thereof.
An HLA-DR antigen which is associated with HLA-DRB1 CHAINS encoded by DRB1*04 alleles.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
An HLA-DR antigen which is associated with HLA-DRB1 CHAINS encoded by DRB1*03 alleles.
The major human blood type system which depends on the presence or absence of two antigens A and B. Type O occurs when neither A nor B is present and AB when both are present. A and B are genetic factors that determine the presence of enzymes for the synthesis of certain glycoproteins mainly in the red cell membrane.
A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an N-terminal catalytic domain and a C-terminal PROLINE-rich domain. The phosphatase subtype is predominantly expressed in LYMPHOCYTES and plays a key role in the inhibition of downstream T-LYMPHOCYTE activation. Polymorphisms in the gene that encodes this phosphatase subtype are associated with a variety of AUTOIMMUNE DISEASES.
Tests that are dependent on the clumping of cells, microorganisms, or particles when mixed with specific antiserum. (From Stedman, 26th ed)
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
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)
A family of cell-surface proteins found on ANTIGEN-PRESENTING CELLS. B7 antigens are ligands for specific cell surface receptor subtypes found on T-CELLS. They play an immunomodulatory role by stimulating or inhibiting the T-CELL activation process.
Tumors or cancer of the PROSTATE.
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.
A member of the tumor necrosis factor receptor superfamily found on most T-LYMPHOCYTES. Activation of the receptor by CD70 ANTIGEN results in the increased proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*24 allele family.
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.
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.
Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.
Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.
Injections into the lymph nodes or the lymphatic system.
A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.
Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)
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.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
The transference of a heart from one human or animal to another.
Proteins found in any species of bacterium.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.

The CTLA-4 gene is expressed in placental fibroblasts. (1/1386)

In order to elucidate the mechanisms that ensure survival of the allogeneic fetus, we are investigating the expression pattern of genes that are involved in peripheral self-tolerance in tissues at the maternal-fetal interface. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a negative regulator of T cell activation and may modulate peripheral self-tolerance. Previously, we reported the preferential transmission of maternally-inherited shorter alleles at a 3'-UTR microsatellite locus to liveborn children, but random transmission of paternally-inherited alleles, suggesting that CTLA-4 may be involved in the maintenance of tolerance at the maternal-fetal interface. In this report, we demonstrate that CTLA-4 mRNA and protein are indeed expressed in fetal tissues at the maternal-fetal interface throughout gestation.  (+info)

Cellular and molecular characterization of the scurfy mouse mutant. (2/1386)

Mice hemizygous (Xsf/Y) for the X-linked mutation scurfy (sf) develop a severe and rapidly fatal lymphoproliferative disease mediated by CD4+CD8- T lymphocytes. We have undertaken phenotypic and functional studies to more accurately identify the immunologic pathway(s) affected by this important mutation. Flow cytometric analyses of lymphoid cell populations reveal that scurfy syndrome is characterized by changes in several phenotypic parameters, including an increase in Mac-1+ cells and a decrease in B220+ cells, changes that may result from the production of extremely high levels of the cytokine granulocyte-macrophage CSF by scurfy T cells. Scurfy T cells also exhibit strong up-regulation of cell surface Ags indicative of in vivo activation, including CD69, CD25, CD80, and CD86. Both scurfy and normal T cells are responsive to two distinct signals provided by the TCR and by ligation of CD28; scurfy cells, however, are hyperresponsive to TCR ligation and exhibit a decreased requirement for costimulation through CD28 relative to normal controls. This hypersensitivity may result, in part, from increased costimulation through B7-1 and B7-2, whose expression is up-regulated on scurfy T cells. Although the specific defect leading to this hyperactivation has not been identified, we also demonstrate that scurfy T cells are less sensitive than normal controls to inhibitors of tyrosine kinases such as genistein and herbimycin A, and the immunosuppressant cyclosporin A. One interpretation of our data would suggest that the scurfy mutation results in a defect, which interferes with the normal down-regulation of T cell activation.  (+info)

Experimental murine schistosomiasis in the absence of B7 costimulatory molecules: reversal of elicited T cell cytokine profile and partial inhibition of egg granuloma formation. (3/1386)

The granulomatous inflammation in infection with the helminth Schistosoma mansoni represents a cellular hypersensitivity reaction mediated by, and dependent upon, MHC class II-restricted CD4+ Th cells sensitized to parasite egg Ags. The current work examines the role and significance of the B7:CD28/CTLA-4 pathway in providing the costimulation necessary for the activation of these pathogenic T cells. In vitro T cell responses in B7-1-/- mice, 7-8 wk postinfection, were no different from wild-type controls, but the absence of B7-2 molecules resulted in a decrease in egg Ag-induced proliferation with increased IFN-gamma production. Both B7-1-/- and B7-2-/- mice exhibited intact granuloma formation. In contrast, CD4+ Th cells from B7-1/2 double-deficient mice displayed a dramatic loss of proliferative capacity upon stimulation with egg Ag. Most strikingly, these T cells secreted only IFN-gamma, but not IL-4 and IL-10, a pattern entirely opposite to that displayed by wild-type controls. Despite these major differences in T cell reactivity, B7-1/2-/- mice had only a limited reduction of granuloma size and fibrosis, without appreciable difference in cellular composition. These results show that substantial granuloma formation can occur under conditions of limited T cell expansion and restricted Th1-type cytokine production. They also support the notion that the combined effect of B7 signaling is not as critical for Th1 cell activation as it is for the development of the Th2 dominant environment characteristic of the evolving schistosome infection in H-2b mice.  (+info)

Prevention of autoimmune recurrence and rejection by adenovirus-mediated CTLA4Ig gene transfer to the pancreatic graft in BB rat. (4/1386)

Type 1 diabetes is the result of a selective destruction of pancreatic islets by autoreactive T-cells. Therefore, in the context of islet or pancreas transplantation, newly transplanted beta-cells are threatened by both recurrent autoimmune and alloimmune responses in recipients with type 1 diabetes. In the present study, using spontaneously diabetic BB rats, we demonstrate that whereas isolated islets are susceptible to autoimmune recurrence and rejection, pancreaticoduodenal grafts are resistant to these biological processes. This resistance is mediated by lymphohematopoietic cells transplanted with the graft, since inactivation of these passenger cells by irradiation uniformly rendered the pancreaticoduodenal grafts susceptible to recurrent autoimmunity. We further studied the impact of local immunomodulation on autoimmune recurrence and rejection by ex vivo adenovirus-mediated CTLA4Ig gene transfer to pancreaticoduodenal grafts. Syngeneic DR-BB pancreaticoduodenal grafts transduced with AdmCTLA4Ig were rescued from recurrent autoimmunity. In fully histoincompatible LEW-->BB transplants, in which rejection and recurrence should be able to act synergistically, AdmCTLA4Ig transduced LEW-pancreaticoduodenal allografts enjoyed markedly prolonged survival in diabetic BB recipients. In situ reverse transcription-polymerase chain reaction revealed that transferred CTLA4Ig gene was strongly expressed in both endocrine and exocrine tissues on day 3. These results indicate the potential utility of local CD28-B7 costimulatory blockade for prevention of alloimmune and autoimmune destruction of pancreatic grafts in type 1 diabetic hosts.  (+info)

Phenotypic analysis of lymphocytes and monocytes/macrophages in peripheral blood and bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis. (5/1386)

BACKGROUND: The granulomatous inflammation in sarcoidosis is driven by the interplay between T cells and macrophages. To gain a better understanding of this process the expression by these cells of cell surface activation markers, co-stimulatory molecules, and adhesion molecules was analysed. METHODS: CD4+ and CD8+ T lymphocytes from peripheral blood (PBL) or bronchoalveolar lavage (BAL) fluid, as well as paired peripheral blood monocytes and alveolar macrophages from 27 patients with sarcoidosis were analysed by flow cytometry. RESULTS: CD26, CD54, CD69, CD95, and gp240 were all overexpressed in T cells from BAL fluid compared with those from PBL in both the CD4+ and CD8+ subsets, while CD57 was overexpressed only in BAL CD4+ cells. In contrast, CD28 tended to be underexpressed in the BAL T cells. Monocyte/macrophage markers included CD11a, CD11b, CD11c, CD14, CD16, CD54, CD71, CD80 and CD86 and HLA class II. CD11a expression in alveolar macrophages (and peripheral blood monocytes) was increased in patients with active disease and correlated positively with the percentage of BAL lymphocytes. Expression of CD80 in macrophages correlated with the BAL CD4/CD8 ratio. CONCLUSIONS: Our data indicate substantial activation of both CD4+ and CD8+ lung T cells in sarcoidosis. There were also increased numbers of BAL lymphocytes whose phenotypic characteristics have earlier been associated with clonally expanded, replicatively senescent cells of the Th1 type.  (+info)

The role of CTLA-4 in the regulation of T cell immune responses. (6/1386)

Over the past few years a great deal of research has examined how T cell-dependent immune responses are initiated and subsequently regulated. Ligation of the TCR with an antigenic peptide bound to an MHC protein on a professional APC provides the crucial antigen-specific stimulus required for T cell activation. Interaction of CD28 with CD80 or CD86 molecules on APC initiates a costimulatory or second signal within the T cell which augments and sustains T cell activation initiated through the TCR. However, recently it has become clear that T cell immune responses are a result of a balance between stimulatory and inhibitory signals. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a cell surface molecule that is expressed nearly exclusively on CD4+ and CD8+ T cells. Investigation into the role of CTLA-4 in the regulation of T cell immune responses has revealed that CTLA-4 is a very important molecule involved in the maintenance of T cell homeostasis. In the present review, evidence for the proposed inhibitory role of CTLA-4 is examined and a model suggesting a role for CTLA-4 in both early and late stages of T cell activation is presented.  (+info)

CTLA-4 gene polymorphism is associated with predisposition to coeliac disease. (7/1386)

BACKGROUND: Susceptibility to coeliac disease is strongly associated with particular HLA class II alleles. However, non-HLA genetic factors are likely to be required for the development of the disease. Among candidate genes is the CTLA-4 (cytotoxic T lymphocyte associated) gene located on chromosome 2q33 in humans, which encodes a cell surface molecule providing a negative signal for T cell activation. AIMS: To investigate CTLA-4 exon 1 polymorphism (position 49 A/G) in patients with coeliac disease. PATIENTS: 101 patients with coeliac disease and 130 healthy controls. METHODS: Allele specific hybridisation and restriction enzyme digestion of polymerase chain reaction amplified genomic DNA. RESULTS: The A allele of the CTLA-4 position 49 polymorphism was found on 82.2% of chromosomes in patients with coeliac disease compared with 65.8% in controls (p < 0.0001), mostly in the homozygous form (68.3% in patients versus 47.7% in controls; odds ratio (OR) 2.36, 95% confidence interval (CI) 1.37 to 4.06, p = 0.002). Four patients only had the G/G genotype compared with 21 controls (OR 0.21, CI 10.07 to 0.64, p = 0.002). These differences were maintained when subjects were stratified according to the HLA class II phenotype, in particular when patients and controls were matched for the presence of the predisposing HLA DQB1*02 (DQ2) allele or HLA-DQA1*0501/DQB1*02 heterodimer. CONCLUSION: The CTLA-4 gene polymorphism is a non-HLA determinant that predisposes to coeliac disease. Whether it directly contributes to disease susceptibility or represents a marker for a locus in linkage disequilibrium with CTLA-4 needs further investigation.  (+info)

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can regulate dendritic cell-induced activation and cytotoxicity of CD8(+) T cells independently of CD4(+) T cell help. (8/1386)

The mechanisms that regulate the strength and duration of CD8(+) cytotoxic T cell activity determine the effectiveness of an antitumor immune response. To better understand the antitumor effects of anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody treatment, we analyzed the effect of CTLA-4 signaling on CD8(+) T cells in vitro and in vivo. In vitro, cross-linking of CTLA-4 on purified CD8(+) T cells caused decreased proliferative responses to anti-CD3 stimulation and rapid loss of activation marker expression. In vivo, blockade of CTLA-4 by neutralizing anti-CTLA-4 mAb greatly enhanced the accumulation, activation, and cytotoxic activity of CD8(+) T cells induced by immunization with Ag on dendritic cells (DC). This enhanced response did not require the expression of MHC class II molecules on DC or the presence of CD4(+) T cells. These results demonstrate that CTLA-4 blockade is able to directly enhance the proliferation and activation of specific CD8(+) T cells, indicating its potential for tumor immunotherapy even in situations in which CD4(+) T cell help is limited or absent.  (+info)

The blockade of immune checkpoints, such as programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), is a promising novel approach in cancer treatment. As these pathways are non-redundant, dual targeting may have additive or synergistic antitumour activity. Durvalumab (MEDI4736) is a selective, high affinity human IgG1 mAb that blocks programmed cell death ligand-1 (PD-L1) binding to PD-1 (IC50 0.1 nM) and CD80 (IC50 0.04 nM), and tremelimumab is a selective human IgG2 mAb inhibitor of CTLA-4. In a Phase 1b study (NCT02000947), durvalumab + tremelimumab has shown encouraging clinical activity (objective response rate [ORR] 33% [95% CI 17-54%] across tremelimumab 1 mg/kg cohorts [n = 27]) and manageable tolerability in patients (pts) with both PD-L1-positive and -negative NSCLC. NEPTUNE is a Phase 3 study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy versus standard of care (SoC) platinum-based doublets in the first-line ...
Cancer immunotherapy relies on the ability of the immune system to target tumor specific antigens to generate an immune response. This initial response requires both binding of the MHC/antigen peptide to T-cell receptor complex along with a second co-stimulatory signal created by the binding of CD28 on the T cell with B7 located on the antigen presenting cell. Regulatory checkpoints, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), serve to attenuate this signal, thereby preventing autoimmunity. Its key role in regulating the immune system has made CTLA-4 an attractive therapeutic target for cancer, with the development of fully human monoclonal antibodies that have successfully targeted CTLA-4 in clinical trials. Augmentation of the immune response via blockade of CTLA-4 represents a significant advance in the field of oncology and has demonstrated an improvement in survival for patients with metastatic melanoma. An increased understanding of the components of this pathway and the ...
Immune checkpoint inhibitors (ICIs), including antibodies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1), have shown durable treatment...
Background: Associations between polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) / interleukin-18 (IL-18) and susceptibility to liver diseases were already reported by many publications. The aim of this meta-analysis was to clarify associations between polymorphisms in CTLA-4/IL-18 and liver diseases by combing the results of all relevant publications. Methods: Eligible publications were searched from Pubmed, Embase, WOS and CNKI. The latest literature searching update was performed on 2nd October, 2019. We used Review Manager to combine the results of individual studies. Results: Sixty-seven studies were included in this study. Combined results revealed that CTLA-4 rs231775 (dominant comparison: OR 0.83, 95 % CI 0.79-0.88; recessive comparison: OR 1.33, 95 % CI 1.23-1.43; allele comparison: OR 0.84, 95 % CI 0.78-0.90), IL-18 rs1946518 (dominant comparison: OR 0.85, 95 % CI 0.78-0.92; recessive comparison: OR 1.29, 95 % CI 1.13-1.48; allele comparison: OR 0.79, 95 % CI ...
The emergence of immune checkpoint inhibitors for solid tumor treatments represents a major oncological advance. Since the approval of ipilimumab, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody, for the treatment of metastatic melanoma, many drugs, especially those targeting PD1/PD-L1, have demonstrated promising antitumor effects in many types of cancer. By reactivating the immune system (IS), these immunotherapies have led to the development of new toxicity profiles, also called immune-related adverse events (irAEs). IrAEs can involve many organ systems, and their management is radically different from that of cytotoxic drugs; irAEs require immunosuppressive treatments, such as corticoids or tumor necrosis factor alpha (TNFα) antibody. Additionally, the occurrence of irAEs has raised significant questions. Here, we summarize progress that has been made toward answering these questions, focusing on 1) the impact of immunotherapy dose on irAE occurrence, 2) the correlation ...
Researchers have found that sometimes the body’s own immune system may slow down or control cancer growth. Sometimes this natural immune system response stops, and the cancer is not killed by the immune system. Research has shown that, in some patients, cancer cells and immune cells start to express signals that stop the body’s immune system from killing the cancer. New drugs being developed are designed to block these signals and to increase the immune response. Durvalumab and tremelimumab are two of these drugs. Both drugs are antibodies (proteins that are produced by the body’s defense system). Durvalumab given by itself or with tremelimumab may boost the ability of your immune system to detect and fight cancer. Each of these drugs targets a different signal. Durvalumab targets a signal on cancer cells called Programmed Cell Death Ligand 1 (PD-L1) and tremelimumab targets a signal on immune cells called Cytotoxic T-Lymphocyte-associated Antigen 4 (CTLA-4). It is hoped that ...
Researchers have found that sometimes the body’s own immune system may slow down or control cancer growth. Sometimes this natural immune system response stops, and the cancer is not killed by the immune system. Research has shown that, in some patients, cancer cells and immune cells start to express signals that stop the body’s immune system from killing the cancer. New drugs being developed are designed to block these signals and to increase the immune response. Durvalumab and tremelimumab are two of these drugs. Both drugs are antibodies (proteins that are produced by the body’s defense system). Durvalumab given by itself or with tremelimumab may boost the ability of your immune system to detect and fight cancer. Each of these drugs targets a different signal. Durvalumab targets a signal on cancer cells called Programmed Cell Death Ligand 1 (PD-L1) and tremelimumab targets a signal on immune cells called Cytotoxic T-Lymphocyte-associated Antigen 4 (CTLA-4). It is hoped that ...
Immune checkpoint therapies have attracted amounts of attention from scientists who are devoted to cancer treatment. What is immune checkpoint? It is a kind of co-stimulatory and inhibitory signal for regulating the antigen recognition of T cell receptor (TCR) in the process of immune responce. When immune system is attacking pathogens, these immune checkpoint molecules can protect the normal tissues from damage. The cancer cells cleverly escape from immune attack by dysregulating immune checkpoint related proteins. Immune checkpoint therapy relys on functioning immune system with agonists of co-stimulatory signals or antagonists of inhibitory signals. Over these years there are two immune checkpoint receptors that have been actively studied: cytotoxic T‑lymphocyte-associated antigen 4 (CTLA-4 / CD152) and programmed cell death protein 1 (PD1 / PDCD1 / CD279). The corresponding antibodies can inhibit the functioning of the receptors and enhance antitumour immunity. Furthermore, multiple ...
This medicine is human anti-CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) monoclonal antibody. It binds to CTLA-4 receptor of T-cell (immune cell) to enhance growth/activation/cytotoxic activity of tumor antigen-specific T-cell. It consequently suppresses tumor growth. It also decreases regulatory T-cell (Treg) function and reduces the number of Treg in the tumor tissue. It consequently increases anti-tumor immune response and suppresses tumor growth ...
Background: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. Objective: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. Methods: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. Results: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%;median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16%(n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal ...
The combined results show that the efficacy of therapeutic vaccination against experimental melanoma is markedly increased by interfering with mechanisms that normally keep autoimmune responses in check. Antitumor treatment is strongly improved if vaccination is either accompanied by CTLA-4 blockade or preceded by a depletion of CD25+ Treg cells. These intervention strategies act synergistically, in that combination of CTLA-4 blockade and depletion of CD25+ Treg cells results in maximal efficacy of therapeutic vaccination. The potency of the different treatment modalities for preventing B16 melanoma outgrowth strongly correlates with the extent of autoimmune skin depigmentation in the treated mice as well as with the frequency of TRP-2180-188-specific CTLs detected in the periphery. Furthermore, antitumor protection was abrogated upon depletion of the CD8+ T cell subset. Therefore, our data indicate that the CTL response against melanoma-associated autoantigens is an important component of the ...
This phase I clinical investigation was undertaken in an effort to obtain a preliminary assessment of the biologic activity and toxicity of MDX-CTLA-4 in previously vaccinated metastatic melanoma and ovarian carcinoma patients. The study was motivated by compelling preclinical data indicating that the combination of CTLA-4 antibody blockade and cancer vaccination stimulated greater levels of antitumor immunity than either approach alone. Because the combination treatment also provoked a loss of tolerance to normal differentiation antigens, the risk of serious toxicities to patients was of some concern. Hence, we initially elected to administer CTLA-4 antibody blockade to previously vaccinated cancer patients.. Our initial results suggest that a single infusion of MDX-CTLA-4 may be safely delivered in this clinical setting. The generation of low titers of autoantibodies shows that the therapy may at least partially compromise systemic tolerance, but no evidence for autoimmune disease was noted. ...
This phase I clinical investigation was undertaken in an effort to obtain a preliminary assessment of the biologic activity and toxicity of MDX-CTLA-4 in previously vaccinated metastatic melanoma and ovarian carcinoma patients. The study was motivated by compelling preclinical data indicating that the combination of CTLA-4 antibody blockade and cancer vaccination stimulated greater levels of antitumor immunity than either approach alone. Because the combination treatment also provoked a loss of tolerance to normal differentiation antigens, the risk of serious toxicities to patients was of some concern. Hence, we initially elected to administer CTLA-4 antibody blockade to previously vaccinated cancer patients.. Our initial results suggest that a single infusion of MDX-CTLA-4 may be safely delivered in this clinical setting. The generation of low titers of autoantibodies shows that the therapy may at least partially compromise systemic tolerance, but no evidence for autoimmune disease was noted. ...
Our findings support the hypothesis that T cell activation is a critical and proximal event in the complex chronic inflammatory cascade that culminates in the generation of psoriatic plaques. To our knowledge, this is the first report documenting the accumulation of mature DCs in a human autoimmune target organ, the skin. Additionally, the resolution of activated phenotypes on lesional keratinocytes, DCs, and vascular endothelium after T cell costimulatory blockade has not previously been reported. Thus, these data expand upon our prior observations (15) and provide possible mechanisms for the observed durable reduction in intralesional T cells after administration of CTLA4Ig. We have demonstrated that a reduced capacity for lesional T cell clonal expansion (due to reversion of the lesional skin APC population to a less mature/immunocompetent state) and decreased vascular recruitment may both have been contributory factors. These observations suggest that clinical activity in this chronic ...
Immunotherapy encompasses both vaccines that direct immune responses to tumor-associated antigens, and checkpoint blocking antibodies that inhibit immune system suppression by targeting key pathways mediated by cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 (PD-1), and programmed de …
There is not evidence to support a synergistic effect of CTLA-4 blockade plus IL-2 administration, because the 22% objective response rate is that expected from the sum of these two agents administered alone. Durable cancer regressions were seen in patients treated with this combination.
Within the paradigm of the two-signal model of lymphocyte activation, the interest in costimulation has witnessed a remarkable emergence in the past few years with the discovery of a large array of molecules that can serve this role, including some with an inhibitory function. Interest has been further enhanced by the realization of these molecules potential as targets to modulate clinical immune responses. Although the therapeutic translation of mechanistic knowledge in costimulatory molecules has been relatively straightforward, the capacity to target their inhibitory counterparts has remained limited. This limited capacity is particularly apparent in the case of the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), a major negative regulator of T cell responses. Because there have been several previous comprehensive reviews on the function of this molecule, we focus here on the physiological implications of its structural features. Such an exercise may ultimately help us to design
Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.. ...
Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.. ...
Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.. ...
Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.. ...
Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.. ...
Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.. ...
Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.. ...
Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.. ...
Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.. ...
Immune checkpoint factors, such as programmed cell death protein-1/2 (PD-1, PD-2) or cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) receptors, are targets for monoclonal antibodies (MAbs) developed for cancer immunotherapy. Indeed, modulating immune inhibitory pathways has been considered an important breakthrough in cancer treatment. Although immune checkpoint blockade therapy used to treat malignant diseases has provided promising results, both solid and haematological malignancies develop mechanisms that enable themselves to evade the host immune system. To overcome some major limitations and ensure safety in patients, recent strategies have shown that combining epigenetic modulators, such as inhibitors of histone deacetylases (HDACi) or DNA methyltransferases (DNMTi), with immunotherapeutics can be useful. Preclinical data generated using mouse models strongly support the feasibility and effectiveness of the proposed approaches. Indeed, co-treatment with pan- or class I-selective HDACi or
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PRIMARY OBJECTIVES:. I. Determine the maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) (ipilimumab) administered with sargramostim (GM-CSF) in patients with metastatic androgen-independent prostate cancer. (Phase I) II. Determine the safety of this regimen in these patients. (Phase I) III. Evaluate the efficacy as measured by reduction in PSA associated with combining GM-CSF with CTLA-4 blockade with ipilimumab at a dosage of 3 mg/kg given monthly x 6 doses (d1 of courses 1-6). (Cohort Expansion). SECONDARY OBJECTIVES:. I. Determine the T-cell immunity and T-cell response in patients treated with this regimen. (Phase I) II. Determine the pharmacokinetics of MDX-010 in these patients. (Phase I) III. Determine the prostate-specific antigen and/or objective responses in patients treated with this regimen. (Phase I) IV. Determine the percentages of activated, naive, and memory T-cells. (Cohort Expansion) V. Determine the measurement of T-cell ...
PRIMARY OBJECTIVES:. I. Determine the maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) (ipilimumab) administered with sargramostim (GM-CSF) in patients with metastatic androgen-independent prostate cancer. (Phase I) II. Determine the safety of this regimen in these patients. (Phase I) III. Evaluate the efficacy as measured by reduction in PSA associated with combining GM-CSF with CTLA-4 blockade with ipilimumab at a dosage of 3 mg/kg given monthly x 6 doses (d1 of courses 1-6). (Cohort Expansion). SECONDARY OBJECTIVES:. I. Determine the T-cell immunity and T-cell response in patients treated with this regimen. (Phase I) II. Determine the pharmacokinetics of MDX-010 in these patients. (Phase I) III. Determine the prostate-specific antigen and/or objective responses in patients treated with this regimen. (Phase I) IV. Determine the percentages of activated, naive, and memory T-cells. (Cohort Expansion) V. Determine the measurement of T-cell ...
In this study, we show that bispecific tandem ScFv against human CTLA-4 can have an unexpected biological effect by revealing the plasticity for signaling through the cytoplasmic domain of this surface receptor. On one hand, when CTLA-4 binds B7.1 or B7.2 in the context of coligation with the TCR, it transduces a signal that inhibits T cell activation (reviewed in Refs. 1 , 2 , and 4, 5, 6). On the other hand, we show in this study that binding of a bispecific tandem ScFv ligand of CTLA-4 causes the same cytoplasmic domain to transduce a signal that, by itself, activates the T cell without the need for coligation of the TCR. Although triggered by different ligands that bind to different sites on CTLA-4, both responses involve PP2A. The inhibitory function of CTLA-4 correlates with a decrease in its association with PP2A (19), while the activating function of CTLA-4 correlates with an increase in its association with PP2A.. Activation of T cells by 24:26 is not the result of functional blockade ...
CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4, CD152) protein. CTLA4 blocking antibodies are used in cancer therapy (immune checkpoint blockade therapy). Space-filling model with conventional colour coding. - Stock Image F019/2238
CTLA-4 został zidentyfikowany w bibliotece cDNA mysich limfocytów T cytotoksycznych w 1987 roku. Na podstawie analizy sekwencji nukleotydowych oraz przewidywanej sekwencji aminokwasowej odkrywcy zaklasyfikowali CTLA-4 do białek nadrodziny immunoglobulin[5]. Ludzki gen CTLA-4 zawiera 4 egzony[2]. Wykazano silne podobieństwo sekwencji nukleotydowej i aminokwasowej CTLA-4 do CD28, innego białka szeroko występującego na limfocytach T. Zarówno u myszy, jak i u człowieka obydwa geny znajdują się na tym samym chromosomie i w bezpośrednim sąsiedztwie, co wskazuje na pochodzenie od jednego genu, który uległ duplikacji[6]. Zgodnie z wnioskami wynikającymi z analizy sekwencji, model struktury mysiego CTLA-4 opublikowany na bazie badań krystalograficznych w 2000 roku wskazuje, że białko to należy do nadrodziny immunoglobulin i posiada topologię części zmiennej[1].. CTLA-4 występuje w formie homodimeru, przy czym podjednostki są połączone mostkiem siarczkowym między cysteinami 120 ...
A soluble fusion protein consisting of the extracellular domain of human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1) with immunosuppressive activity. Abatacept binds CD80 and CD86 on antigen presenting cells (APCs), blocking interaction with CD28 on T lymphocytes, which initiates a co-stimulatory signal required for full activation of T lymphocytes.
|em|Background:|/em| Asthma is an immunological disorder in which T helper 2 (Th2)-type cells and inflammatory cytokines have a prominent role in its pathogenesis. B- and T-lymphocyte attenuator (BTLA), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. |em|Objective:|/em| In the present study of asthmatic patients we measured the soluble isoforms of BTLA (sBTLA), CTLA-4 (sCTLA-4) and PD-1 (sPD-1) in induced sputum fluid with the aim to evaluate their utility as responsible for exacerbation. |em|Methods:|/em| Eighty patients with asthma and 30 healthy controls (HC) were included in the study. Sputum fluid concentrations of sBTLA, sCTLA-4 and sPD-1 were measured with ELISA. Comparisons were made with Mann-Whitney U test and correlations with IL-17, IL-26 levels and FEV1 (%) were assessed with Spearmans Rank correlation test. |em|Results:|/em| sBTLA levels were significantly higher in the severe and moderate
TY - JOUR. T1 - Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. AU - Ma, Weijie. AU - Gilligan, Barbara M.. AU - Yuan, Jianda. AU - Li, Tianhong. PY - 2016/5/27. Y1 - 2016/5/27. N2 - Modulating immune inhibitory pathways has been a major recent breakthrough in cancer treatment. Checkpoint blockade antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programed cell-death protein 1 (PD-1) have demonstrated acceptable toxicity, promising clinical responses, durable disease control, and improved survival in some patients with advanced melanoma, non-small cell lung cancer (NSCLC), and other tumor types. About 20 % of advanced NSCLC patients and 30 % of advanced melanoma patients experience tumor responses from checkpoint blockade monotherapy, with better clinical responses seen with the combination of anti-PD-1 and anti-CTLA-4 antibodies. Given the power of these new therapies, it is important to understand the ...
Novus Biologicals Human CTLA-4 ELISA Kit 96 Tests Electrophoresis, Western Blotting and ELISA:ELISA Reagents, Plates and Accessories:ELISA Kits:C-E ELISA Kits
Our results support the concept that variants in CTLA4 provide the basis for a novel Mendelian form of early-onset CD associated with systemic autoimmunity. Incomplete penetrance of autoimmunity further indicates the presence of other genetic and/or environmental modifiers.A novel missense variant was identified in CTLA4 encoding CTLA-4, a coinhibitory protein expressed by T cells and required for regulation of T cell activation. The residue affected by the mutation, CTLA-4 Tyr60, is evolutionarily highly conserved, and the identified Y60C variant is predicted to affect protein folding and structural stability and demonstrated to cause impaired CTLA-4 dimerisation and CD80 binding. Intestinal inflammation and autoimmunity in carriers of CTLA-4 Y60C exhibit incomplete penetrance with a spectrum of clinical presentations ranging from asymptomatic carrier status to fatal autoimmunity and intestinal inflammation. In a clinically affected CTLA-4 Y60C carrier, T cell proliferation was increased in ...
The 51Cr release assay has traditionally been used to investigate effector cell cytotoxic function against labeled targets, but this method has inherent problems that include hazards associated with radioactivity, cell labeling and high spontaneous release. Here we describe a novel flow cytometric assay which addresses and improves upon the problems currently encountered with the 51Cr release assay. The fluorometric assessment of T lymphocyte antigen specific lysis (FATAL) assay employs dual staining (PKH-26 and CFSE) to identify and evaluate the target population. We found that the PKH-26/CFSE combination efficiently labeled target cells. Evaluation of the spontaneous leakage from dye labeled target cells was forty fold lower than the spontaneous leakage seen with the 51Cr release assay. The FATAL assay permitted a more accurate assessment of the effector: target ratio, and detected low levels of cytotoxic T lymphocyte (CTL) mediated lysis. There was a strong correlation between the 51Cr release and
Tremelimumab (formerly ticilimumab, CP-675,206) is a fully human monoclonal antibody against CTLA-4. It is an immune checkpoint blocker. Previously in development by Pfizer, it is now in investigation by MedImmune, a wholly owned subsidiary of AstraZeneca. It has been undergoing human trials for the treatment of various cancers but has not attained approval for any. Tremelimumab aims to stimulate an immune system attack on tumors. Cytotoxic T lymphocytes (CTLs) can recognize and destroy cancer cells. However, there is also an inhibitory mechanism (immune checkpoint) that interrupts this destruction. Tremelimumab turns off this inhibitory mechanism and allows CTLs to continue to destroy the cancer cells. This is immune checkpoint blockade. Tremelimumab binds to the protein CTLA-4, which is expressed on the surface of activated T lymphocytes and inhibits the killing of cancer cells. Tremelimumab blocks the binding of the antigen-presenting cell ligands B7.1 and B7.2 to CTLA-4, resulting in ...
Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, ...
A high mutational load and the presence of a T-cell-inflamed environment may independently predict for treatment response to pembrolizumab (Keytruda) and progression-free survival, according to a study presented by Tanguy Seiwert, MD, of the University of Chicago, at the 2017 ASCO-SITC Clinical Immuno-Oncology Symposium.1. Nonsynonymous mutational load and neoantigen load as well as an 18-gene immune-related gene-expression profiling were significantly associated with overall response and progression-free survival to pembrolizumab across multiple indications, Dr. Seiwert revealed. This suggests that tumor antigenicity and T-cell infiltration may provide complementary information for expected pembrolizumab activity and may be useful in characterizing responses to immunotherapies, he said.. Tumor mutational load has been shown to correlate with benefit from drugs blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) in multiple tumor types. ...
Genes and mechanisms involved in common complex diseases, such as the autoimmune disorders that affect approximately 5% of the population, remain obscure. Here we identify polymorphisms of the cytotoxic T lymphocyte antigen 4 gene (CTLA4)--which encodes a vital negative regulatory molecule of the immune system--as candidates for primary determinants of risk of the common autoimmune disorders Graves disease, autoimmune hypothyroidism and type 1 diabetes. In humans, disease susceptibility was mapped to a non-coding 6.1 kb 3 region of CTLA4, the common allelic variation of which was correlated with lower messenger RNA levels of the soluble alternative splice form of CTLA4. In the mouse model of type 1 diabetes, susceptibility was also associated with variation in CTLA-4 gene splicing with reduced production of a splice form encoding a molecule lacking the CD80/CD86 ligand-binding domain. Genetic mapping of variants conferring a small disease risk can identify pathways in complex disorders, as exemplified
The administration of anti-CTLA-4 Ab to patients with metastatic melanoma induced durable objective clinical responses that were highly associated with the induction of autoimmune side effects (23, 24). However, the mechanism responsible for tumor regression and autoimmunity was unclear, although two dominant hypotheses have been proposed. CTLA-4 is constitutively expressed on CD4+CD25+ T regulatory cells (25, 26); hence, the administration of an anti-CTLA-4 Ab may lead to the depletion or inhibition of these regulatory cells, with a resultant increase in the activity of effector T cells. Alternatively, CTLA-4 engagement imparts an inhibitory signal to the T cell (5), and the blockade of CTLA-4 may directly tip the balance toward T cell effector function. These two possibilities have been studied in this report.. We first addressed the impact of anti-CTLA-4 Ab on CD4+CD25+ T cell regulatory cell function in vitro using a coculture suppression assay. This proliferation assay was developed to ...
SS1P is an anti-mesothelin immunotoxin composed of a targeting antibody fragment genetically fused to a truncated fragment of Pseudomonas exotoxin A. Delayed responses reported in mesothelioma patients receiving SS1P suggest that anti-tumor immunity is induced. The goal of this study is to evaluate if SS1P therapy renders mesothelioma tumors more sensitive to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint blockade. We evaluated the ability of SS1P to induce adenosine triphosphate (ATP) secretion and calreticulin expression on the surface of AE17M mouse mesothelioma cells. Both properties are associated with immunogenic cell death. Furthermore, we treated these tumors with intra-tumoral SS1P and systemic CTLA-4. We found that SS1P increased the release of ATP from AE17M cells in a dose and time-dependent manner. In addition, SS1P induced calreticulin expression on the surface of AE17M cells. These results suggest that SS1P promotes immunogenic cell death and could sensitize tumors
Ipilimumab, a novel therapy for metastatic melanoma, inhibits cytotoxic T-lymphocyte apoptosis, causing both antitumor activity and significant autoimmunity, including autoimmune thyroiditis. Steroids are frequently used in treatment of immune-related adverse events; however, a concern regarding the property of steroids to reduce therapeutic antitumor response exists. This study describes the first reported case of ipilimumab-associated thyroid storm and implicates iopanoic acid as an alternative therapy for immune-mediated adverse effects. An 88-year-old woman with metastatic melanoma presented with fatigue, anorexia, decreased functional status, and intermittent diarrhea for several months, shortly after initiation of ipilimumab - a recombinant human monoclonal antibody to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). On arrival, she was febrile, tachycardic, and hypertensive with a wide pulse pressure, yet non-toxic appearing. She had diffuse, non-tender thyromegaly. An ...
TY - JOUR. T1 - Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab. T2 - an Italian melanoma intergroup study. AU - Italian Melanoma Intergroup (IMI). AU - Pistillo, Maria Pia. AU - Fontana, Vincenzo. AU - Morabito, Anna. AU - Dozin, Beatrice. AU - Laurent, Stefania. AU - Carosio, Roberta. AU - Banelli, Barbara. AU - Ferrero, Francesca. AU - Spano, Laura. AU - Tanda, Enrica. AU - Ferrucci, Pier Francesco. AU - Martinoli, Chiara. AU - Cocorocchio, Emilia. AU - Guida, Michele. AU - Tommasi, Stefania. AU - De Galitiis, Federica. AU - Pagani, Elena. AU - Antonini Cappellini, Gian Carlo. AU - Marchetti, Paolo. AU - Quaglino, Pietro. AU - Fava, Paolo. AU - Osella-Abate, Simona. AU - Ascierto, Paolo Antonio. AU - Capone, Mariaelena. AU - Simeone, Ester. AU - Romani, Massimo. AU - Spagnolo, Francesco. AU - Queirolo, Paola. PY - 2018/10/11. Y1 - 2018/10/11. N2 - CTLA-4 blockade by means of ipilimumab (IPI) potentiates the immune response and ...
Tsütotoksiline T-lümfotsüüdi antigeen-4 ehk CTLA-4 ehk CTLA4 ehk CD152 (cytotoxic T-lymphocyte-associated protein 4) on valk, mida ekspresseeritakse mitmete T-rakkude pinnal ja mis toimib T-rakkude aktivatsiooni negatiivse regulaatorina. CTLA4 täpsed funktsioonid pole selged. Arvatakse, et CTLA4 käitub immuunretseptorina ja osaleb immunosupressioonis. Selle molekuli funktsiooniks on immuunsüsteemi toimimise reguleerimine ja see mängib tähtsat rolli autoimmuunhaiguste ära hoidmisel. CTLA4 osaleb tüümuse arengus, uuringud näitavad, et CTLA-4 ekspressioon toimub tüümuse kortikomedullaarses tsoonis. Inimestel kodeerib seda valku CTLA4 geen ja selle mutatsioonidega võib suureneda risk mitmete autoimmuunhaiguste tekkeks, nagu süsteemne erütematoosluupus, Hashimoto türeoidiit, tsöliaakia, thyroid-associated orbitopathy, primaarne biliaartsirroos. CTLA4 soodustab teatud vähirakkude immuunjärelevalvele märkamatuks jäämist. Onkoloogias kasutatakse inimese CTLA-4 vastast ...
In a systematic review and meta-analysis reported in JAMA Oncology, Barroso-Sousa et al evaluated the incidence of endocrine dysfunction in patients receiving currently approved immune checkpoint inhibitors for various advanced solid tumors. Patients who received combination therapy were found to have an increased risk of thyroid dysfunction and hypophysitis.. Study Details. A PubMed search through July 2016 identified 38 randomized clinical trials of ipilimumab (Yervoy; cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] inhibitor), nivolumab (Opdivo; programmed cell death protein 1 [PD-1] inhibitor), pembrolizumab (Keytruda; PD-1 inhibitor), and atezolizumab (Tecentriq; programmed cell death protein ligand [PD-L1] inhibitor), involving a total of 7,551 patients. Regimens were categorized into monotherapy with a PD-1 inhibitor, a CTLA-4 inhibitor, or a PD-L1 inhibitor, and combination therapy with a PD-1 plus CTLA-4 inhibitor. Outcomes of interest were the incidence of all-grade ...
Tuberculosis (TB) is the worlds second most common infectious disease after Human Immunodeficiency Virus Infection/Acquired Immunodeficiency Syndrome (HIV/AID) and the most frequent cause of mortality especially in developing countries. T regulatory (Treg) cells, which have suppressive activity and express forkhead winged-helix family transcriptional repressor p3 (FoxP3), suppress the immune responses against pathogens such as Mycobacterium tuberculosis. There are controversial results regarding the role of FoxP3 expressing cells in the blood of patients with TB.The aim of this study was to evaluate the frequency CD4+ CD25+ Treg cells, and FoxP3 and Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) gene expressions in peripheral blood of patients with tuberculosis and patients with positive tuberculin skin test before and after Peripheral Blood Mononuclear Cells (PBMCs) activation with Purified Protein Derivative (PPD).In this cross-sectional study, Peripheral Mononuclear Cells (PBMCs) were isolated from
The monoclonal antibody UC10-4B9 reacts with CD152, also known as cytotoxic T lymphocyte antigen-4 (CTLA-4), which is a 33 kDa member of the immunoglobin superfamily and is expressed on activated T cells at a low level. CTLA-4 and CD28 have similarities concerning B7 family counter-receptors. While CD28 delivers a costimulary signal in T cell activation, CD152 restricts the progression of T cells to an activated state by inhibiting interleukin 2 (IL-2) secretion and cellular proliferation. A large proportion of CTLA-4 is intracellular localized. For a complete detection it may be necessary to assess intracellular staining in addition to surface expression of CD152. - Liechtenstein
Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are still needed, and resistance mechanisms remain incompletely understood. To address this, we examined a cohort of metastatic melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1) by immunogenomic profile analyses from serial tumor biopsies. From immune profiling (12 marker immunohistochemistry and NanoString Gene Expression Profiling), we found that adaptive immune signatures in tumor biopsies obtained from early on
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner. Autophagy-deficient DCs exhibited reduced immunogenic potential and failed to prime autoantigen-specific CD4+ T cells to mediate autoimmunity. Mechanistically, CTLA4 binding promoted activation of the PI3K/Akt/mTOR axis and FoxO1 nuclear exclusion in DCs, leading to decreased transcription of the autophagy component microtubule-associated protein 1 light chain 3β (Lc3b). Human DCs treated with CTLA4-Ig, a fusion protein ...
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner. Autophagy-deficient DCs exhibited reduced immunogenic potential and failed to prime autoantigen-specific CD4+ T cells to mediate autoimmunity. Mechanistically, CTLA4 binding promoted activation of the PI3K/Akt/mTOR axis and FoxO1 nuclear exclusion in DCs, leading to decreased transcription of the autophagy component microtubule-associated protein 1 light chain 3β (Lc3b). Human DCs treated with CTLA4-Ig, a fusion protein ...
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner. Autophagy-deficient DCs exhibited reduced immunogenic potential and failed to prime autoantigen-specific CD4+ T cells to mediate autoimmunity. Mechanistically, CTLA4 binding promoted activation of the PI3K/Akt/mTOR axis and FoxO1 nuclear exclusion in DCs, leading to decreased transcription of the autophagy component microtubule-associated protein 1 light chain 3β (Lc3b). Human DCs treated with CTLA4-Ig, a fusion protein ...
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner. Autophagy-deficient DCs exhibited reduced immunogenic potential and failed to prime autoantigen-specific CD4+ T cells to mediate autoimmunity. Mechanistically, CTLA4 binding promoted activation of the PI3K/Akt/mTOR axis and FoxO1 nuclear exclusion in DCs, leading to decreased transcription of the autophagy component microtubule-associated protein 1 light chain 3β (Lc3b). Human DCs treated with CTLA4-Ig, a fusion protein ...
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner. Autophagy-deficient DCs exhibited reduced immunogenic potential and failed to prime autoantigen-specific CD4+ T cells to mediate autoimmunity. Mechanistically, CTLA4 binding promoted activation of the PI3K/Akt/mTOR axis and FoxO1 nuclear exclusion in DCs, leading to decreased transcription of the autophagy component microtubule-associated protein 1 light chain 3β (Lc3b). Human DCs treated with CTLA4-Ig, a fusion protein ...
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner. Autophagy-deficient DCs exhibited reduced immunogenic potential and failed to prime autoantigen-specific CD4+ T cells to mediate autoimmunity. Mechanistically, CTLA4 binding promoted activation of the PI3K/Akt/mTOR axis and FoxO1 nuclear exclusion in DCs, leading to decreased transcription of the autophagy component microtubule-associated protein 1 light chain 3β (Lc3b). Human DCs treated with CTLA4-Ig, a fusion protein ...
Immune checkpoints are one of the protective mechanisms in normal organisms. Under the initiation of the usual immune system, T cells can perform antigen-specific cytotoxicity and guide other immune responses against foreign organisms with antigens different from the host itself; however, such functions need to have a set of regulatory functions to avoid causing autoimmune reactions or injuring their own cells or tissues when fighting foreign cells. This set of regulatory functions, which we call immune checkpoint mechanisms, simply means that different groups of ligand and receptor reactions increase or inhibit the immune effects of T cells.. With years experience, Creative BioMart provides a wide range of immune checkpoint proteins and the bio-activity of all those products has been assayed and confirmed, making them essential materials for mechanistic studies and development of new therapeutics.. Creative BioMart immune checkpoint proteins mainly include: 2B4, 4-1BB, 4-1 BB Ligand, B7-1, ...
Immune checkpoints are one of the protective mechanisms in normal organisms. Under the initiation of the usual immune system, T cells can perform antigen-specific cytotoxicity and guide other immune responses against foreign organisms with antigens different from the host itself; however, such functions need to have a set of regulatory functions to avoid causing autoimmune reactions or injuring their own cells or tissues when fighting foreign cells. This set of regulatory functions, which we call immune checkpoint mechanisms, simply means that different groups of ligand and receptor reactions increase or inhibit the immune effects of T cells.. With years experience, Creative BioMart provides a wide range of immune checkpoint proteins and the bio-activity of all those products has been assayed and confirmed, making them essential materials for mechanistic studies and development of new therapeutics.. Creative BioMart immune checkpoint proteins mainly include: 2B4, 4-1BB, 4-1 BB Ligand, B7-1, ...
Immune checkpoints are one of the protective mechanisms in normal organisms. Under the initiation of the usual immune system, T cells can perform antigen-specific cytotoxicity and guide other immune responses against foreign organisms with antigens different from the host itself; however, such functions need to have a set of regulatory functions to avoid causing autoimmune reactions or injuring their own cells or tissues when fighting foreign cells. This set of regulatory functions, which we call immune checkpoint mechanisms, simply means that different groups of ligand and receptor reactions increase or inhibit the immune effects of T cells.. With years experience, Creative BioMart provides a wide range of immune checkpoint proteins and the bio-activity of all those products has been assayed and confirmed, making them essential materials for mechanistic studies and development of new therapeutics.. Creative BioMart immune checkpoint proteins mainly include: 2B4, 4-1BB, 4-1 BB Ligand, B7-1, ...
Immune checkpoints are one of the protective mechanisms in normal organisms. Under the initiation of the usual immune system, T cells can perform antigen-specific cytotoxicity and guide other immune responses against foreign organisms with antigens different from the host itself; however, such functions need to have a set of regulatory functions to avoid causing autoimmune reactions or injuring their own cells or tissues when fighting foreign cells. This set of regulatory functions, which we call immune checkpoint mechanisms, simply means that different groups of ligand and receptor reactions increase or inhibit the immune effects of T cells.. With years experience, Creative BioMart provides a wide range of immune checkpoint proteins and the bio-activity of all those products has been assayed and confirmed, making them essential materials for mechanistic studies and development of new therapeutics.. Creative BioMart immune checkpoint proteins mainly include: 2B4, 4-1BB, 4-1 BB Ligand, B7-1, ...
GZMB - GZMB (untagged)-Human granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1) (GZMB) available for purchase from OriGene - Your Gene Company.
T cells are the driving force that mediates graft-versus-host disease (GVHD) after transplantation. Thus, T cell suppression is key for GVHD treatment. Optimal T cell activation requires interaction between CD28, expressed on T cells, and CD80/CD86, expressed on antigen-presenting cells. Furthermore, activation of the metabolic regulator, mammalian target of rapamycin (mTOR) pathway, is critical for T cell function. Currently, there are FDA-approved medicines that inhibit CD80/CD86 (abatacept and belatacept) and mTOR (sirolimus). However, belatacept treatment unexpectedly led to increased acute organ rejection in a renal transplantation clinical trial, possibly by disrupting the checkpoint receptor cytotoxic T lymphocyte antigen 4, which also binds CD80/CD86. Whether blocking CD28 receptor specifically is a viable option for GVHD is not clear.. Watkins and colleagues evaluated the efficacy of a CD28-blocking antibody fragment (FR104) in a rhesus macaque GVHD model with hematopoietic stem cell ...
In this study we provide the first direct evidence that anti-CTLA-4 therapy elicits an increase in the frequency of ICOS+ T cells to play an important role in mediating antitumor immune responses and tumor rejection. Anti-CTLA-4 therapy permits activation of T cells thus leading to an increased frequency of ICOS+ T cells in cancer patients (15-17, 39). Here, we provide data to show a functional role for ICOS+ T cells and the ICOS/ICOSL pathway in mediating antitumor responses, which should be taken into consideration for further studies aimed at improving the efficacy of anti-CTLA-4 therapy in the treatment of cancer patients.. Anti-CTLA-4 antibodies (ipilimumab, BMS and Tremelimumab, Pfizer) are currently in clinical trials. The ipilimumab antibody was recently shown to lead to improved survival in a subset of patients with advanced melanoma (14). Mechanistic investigations as to why a subset of patients derives benefit or how to improve the numbers of patients who derive benefit are currently ...
article{8be6ed91-fde0-42c0-8856-b5903bfbb308, abstract = {,p,CTLA-4 is important to down-regulating T cell responses and has been implicated in type 1 (insulin dependent) diabetes mellitus in both linkage and association studies. The aim of our study was to relate the polymorphic (AT)(n) microsatellite in the 3 untranslated sequence of the CTLA-4 gene to diabetes risk. We studied 616 consecutively diagnosed 0-34 year-old Swedish patients and 502 matched controls by PCR-based genotyping to determine the length of the 3-end (AT)(n)repeat region of the CTLA-4 gene and categorizing alleles as predominantly monomorphic short (S) or highly polymorphic (in length) long (L) alleles. The odds of type 1 diabetes of subjects with the L/L genotype was estimated to be 1.84 times that of subjects with the S/S genotype (95% CI 1.44-2.73, p=0.002). Further analysis of the long alleles, partitioned into intermediate (I) length and very long (VL) alleles, suggested that L alleles act recessively in conferring ...
TY - JOUR. T1 - Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. AU - Chen, Lieping. AU - Ashe, Stephanie. AU - Brady, William A.. AU - Hellström, Ingegerd. AU - Hellström, Karl Erik. AU - Ledbetter, Jeffrey A.. AU - McGowan, Patrick. AU - Linsley, Peter S.. PY - 1992/12/24. Y1 - 1992/12/24. N2 - Interaction of the B7 molecule on antigen-presenting cells with its receptors CD28 and CTLA-4 on T cells provides costimulatory signals for T cell activation. We have studied the effects of B7 on antitumor immunity to a murine melanoma that expresses a rejection antigen associated with the E7 gene product of human papillomavirus 16. While this E7+ tumor grows progressively in immunocompetent hosts, cotransfection of its cells with B7 led to tumor regression by a B7-dependent immune response mediated by CD8+ cytolytic T lymphocytes. The immune response induced by E7+B7+ tumor cells also caused regression of E7+ B7- tumors at distant sites and ...
Background: Patients with diffuse midline gliomas (DMG), including diffuse intrinsic pontine glioma (DIPG), have dismal outcomes. We previously described the H3.3K27M mutation as a shared neoantigen in HLA-A*02.01+ H3.3K27M+ DMGs. Within the Pacific Pediatric Neuro-Oncology Consortium, we assessed safety and efficacy of an H3.3K27M-targeted peptide vaccine. Patients and Methods: Newly diagnosed patients aged 3-21 years with HLA-A*02.01+ and H3.3K27M+ status were enrolled into Stratum A (DIPG) and Stratum B (non-pontine DMG). Vaccine was administered in combination with poly-ICLC every three weeks for eight cycles, followed by once every six weeks. Immuno-monitoring and imaging occurred every three months. Imaging was centrally reviewed. Immunological responses were assessed in peripheral blood mononuclear cells using mass cytometry. Results: 19 patients enrolled in Stratum A (median age=11 years) and 10 in Stratum B (median age=13 years). There were no grade 4 treatment-related adverse events ...
Heppt, Markus V., Heinzerling, Lucie, Kähler, Katharina C., Forschner, Andrea, Kirchberger, Michael C., Loquai, Carmen, Meissner, Markus, Meier, Friedegund, Terheyden, Patrick, Schell, Beatrice, Herbst, Rudolf, Göppner, Daniela, Kiecker, Felix, Rafei-Shamsabadi, David, Haferkamp, Sebastian, Huber, Margit A., Utikal, Jochen, Ziemer, Mirjana, Bumeder, Irmgard, Pfeiffer, Christiane, Schäd, Susanne G., Schmid-Tannwald, Christoph, Tietze, Julia K., Eigentler, Thomas K. and Berking, Carola (2017) Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition. European Journal of Cancer 82, pp. 56-65 ...
BACKGROUND Checkpoint inhibitor pneumonitis (CIP) is a highly morbid complication of immune checkpoint immunotherapy (ICI), one which precludes the continuation of ICI. Yet, the mechanistic underpinnings of CIP are unknown.METHODS To better understand the mechanism of lung injury in CIP, we prospectively collected bronchoalveolar lavage (BAL) samples in ICI-treated patients with (n = 12) and without CIP (n = 6), prior to initiating first-line therapy for CIP (high-dose corticosteroids). We analyzed BAL immune cell populations using a combination of traditional multicolor flow cytometry gating, unsupervised clustering analysis, and BAL supernatant cytokine measurements.RESULTS We found increased BAL lymphocytosis, predominantly CD4+ T cells, in patients with CIP. Specifically, we observed increased numbers of BAL central memory T cells, evidence of type I polarization, and decreased expression of cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1 in BAL Tregs, ...
Caner immunotherapy relies on immune cells ability to detect and eradicate tumor cells as foreign. Learn more about current developments in cell-based immunotherapy, and immune checkpoint proteins involved in soluble factor-based immunotherapy here! BioLegend develops and manufactures world- class, cutting-edge immunological reagents for biomedical research, offered at an outstanding value.
Immune checkpoint inhibitors are a new class of cancer treatments that help the bodys own immune system recognize and destroy cancer cells. However, activating the immune system may cause a form of autoimmune reaction that can affect any organ or tissue. Most immune-related adverse events (irAE) are mild to moderate and reversible, if detected early and addressed appropriately. These irAE most commonly affect the skin, colon, lungs, liver and endocrine organs, and some can be permanent (hypothyroidism) or life threatening (myocarditis). Non-oncology NPs play an integral role in the care of cancer patients and survivors and NPs in specialties such as dermatology, GI, and endocrinology may be consulted regarding the management of an immune-related adverse event. Equip yourself with knowledge about immunotherapy and immune-related adverse events, so you can communicate with the oncology team and work together to address all the patients medical needs.. Laura Zitella MS, RN, ACNP-BC, AOCN; Nurse ...
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Dr Christian Blank - Netherlands Cancer Institute, Amsterdam, The Netherlands. Dr Blank speaks with ecancer at EADO 2017 about targeting immune checkpoints in melanoma patients with anti-PD1 and anti-CTLA-4 drugs.. Dr Blank describes how immune therapy is better suited to certain patient subtypes, and that combined checkpoint therapy may result in significant response or needless toxicity if applied without understanding the biology of the patient and cancer being treated.. Combinations of PD-1 and CTLA-4 targeted therapies were also discussed by Dr Christoph Hoeller, here.. ecancers filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.. ...
Thank you, Suzanne. On behalf of the study investigators Im very pleased to present the first disclosure of overall survival results from the phase III CHECKMATE 067 trial which explores the efficacy of nivolumab, ipilimumab or the combination of both in patients with previously untreated metastatic melanoma. These are my disclosures.. Manipulation of immune checkpoints such as CTLA4 or PD-1 with targeted antibodies has recently emerged as an effective treatment strategy for multiple cancer types. In the phase II randomised CHECKMATE 069 study the combination of nivolumab, an anti-PD-1, and ipilimumab, an anti-CTLA4, resulted in high rates of response, a median duration of response of at least two years and a favourable two year survival rate of 64%. Back in 2015 we presented the initial results of the present phase III study which showed significant improvements in the co-primary endpoint of progression free survival as well as significant improvements in response for both nivolumab containing ...
Background Abatacept is a fusion protein of human CTLA-4 and the Fc portion of human IgG1. It is believed to be effective in the treatment of rheumatoid arthritis by blocking the co-stimulation of T-cells via blocking CD28-B7 interaction as CTLA-4 binds to both B7.1 (CD80) and B7.2 (CD86). However, the interaction of CD28 with B7 is crucial for the activation of naïve cells, whereas it is unclear whether the action of already activated CD4+ T-cells, which are readily present in established disease, also depend on this interaction. ...
Monoclonal antibodies have been developed as anticancer agents to block immune checkpoint pathways associated with programmed cell death 1 (PD-1) and its ligand PD-L1. However, the high cost of antibodies has encouraged researchers to develop other inhibitor types. Here, biphenyl compounds were conjugated with poly
Click to launch & play an online audio visual presentation by Dr. Jonathan Schoenfeld on Immune checkpoint blockade and head and neck cancer, part of a collection of online lectures.
妙通(上海)生物科技有限公司主要產品有原代細胞(HUVEC、NHDF、NHEK等),血液系統細胞(PBMC、祖細胞、DC細胞等),HepaRG細胞株,間充質干細胞,IPS來源的細胞,無血清凍存液,內皮細胞培養基,間充質干細胞生長和分化培養基,Immune Checkpoints.電話:4008-217-320 歡迎來電洽談合作!
妙通(上海)生物科技有限公司主要產品有原代細胞(HUVEC、NHDF、NHEK等),血液系統細胞(PBMC、祖細胞、DC細胞等),HepaRG細胞株,間充質干細胞,IPS來源的細胞,無血清凍存液,內皮細胞培養基,間充質干細胞生長和分化培養基,Immune Checkpoints.電話:4008-217-320 歡迎來電洽談合作!
To become activated, lymphocyte must engage both antigen and costimulatory ligand on the same antigen-presenting cell. T cell ... When bound to CTLA-4, CD86 can be removed from the surface of an APC and onto the Treg cell in a process called trogocytosis. ... This allows CTLA-4 to outcompete CD28 for CD80/CD86 binding. Between CD80 and CD86, CD80 appears to have a higher affinity for ... Since CTLA-4 binds to CD86 with higher affinity than CD28, the co-stimulation necessary for proper T-cell activation is also ...
"Human prostate tumor antigen-specific CD8+ regulatory T cells are inhibited by CTLA-4 or IL-35 blockade". Journal of Immunology ...
... which can prevent an immune response to self-antigen. In addition to interactions with CD28 and CTLA-4, CD80 is also thought to ... van der Merwe PA, Bodian DL, Daenke S, Linsley P, Davis SJ (February 1997). "CD80 (B7-1) binds both CD28 and CTLA-4 with a low ... If the interaction between an antigen-presenting cell and a T-cell is stable enough, the T-cell can remove the CD80 from the ... CD80 can be found on the surface of various immune cells including B cells, monocytes and antigen-presenting cells (APCs) such ...
... phosphorylates the YVKM motif and regulates PI 3-kinase binding to T-cell antigen CTLA-4". Biochem. Biophys. Res. Commun. 252 ( ... 4 (2): 147-51. doi:10.3121/cmr.4.2.147. PMC 1483892. PMID 16809408. Ohta Y, Haire RN, Amemiya CT, et al. (1996). "Human Txk: ... 12 (4): 937-42. PMID 8632917. Wardenburg JB, Fu C, Jackman JK, et al. (1996). "Phosphorylation of SLP-76 by the ZAP-70 protein- ... 271 (33): 19641-4. doi:10.1074/jbc.271.33.19641. PMID 8702662. Raab M, da Silva AJ, Findell PR, Rudd CE (1997). "Regulation of ...
Tasuku Honjo Kyoto University in Japan for their contributions in advance of PD-1 and CTLA-4 immune checkpoint therapy. The ... cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1). Under normal conditions, the immune system ... "CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition". American Journal of Clinical ... 4 May 2017. Retrieved 19 May 2017. Enger, Eldon; et al. Concepts in Biology' 2007 Ed.2007 Edition. McGraw-Hill. p. 173. ISBN ...
This is also related to hearing the flushing of antigens in the eyes or to attempts to achieve mechanical removal of the ... Additional T cell-associated immune dysregulation may be due to a mutation in CTLA-4. CTLA-4 is essential for the negative ... Mutations tend to be in genes for cytokines (such as IL-7), TCRs, or proteins important for somatic recombination and antigen ... They also have reduced the production of antibodies against antigens. In immunosenescence, here is a change in the individual ...
... was conceived by Allison and Krummel along with CTLA-4's inhibitory role in T cell activation. They were able to demonstrate ... These antigens are recognized by dendritic cells that present the antigens to cytotoxic T lymphocytes (CTLs) in the lymph nodes ... The CTLs recognize the cancer cells by those antigens and destroy them. However, along with the antigens, the dendritic cells ... T cells to target a greater variety of antigens rather than by increasing the number attacking a single antigen. During "cancer ...
This suggests Treg-mediated suppression of antigen presenting cells is a multi-step process. In addition to CTLA-4 CD80/CD86 ... T regulatory cell adhesion to antigen presenting dendritic cell causes sequestration of Fascin-1, an actin-bundling protein ... 26 (4): 389-403. doi:10.1016/j.cytogfr.2015.06.001. PMC 4526340. PMID 26119834. Grothey A, Hashizume R, Sahin AA, McCrea PD ( ... 20 (4): 339-45. doi:10.1016/j.cub.2009.12.035. PMC 3163294. PMID 20137952. Chen, Jiahuan; Ganguly, Anutosh; Mucsi, Ashley D.; ...
In 1996, Allison was the first to show that antibody blockade of a T-cell inhibitory molecule (known as CTLA-4) could lead to ... Allison's research is in molecular immunology of the T-cell antigen receptor complex, co-stimulatory receptors, and other ... In the early 1990s, Jim Allison showed that CTLA-4 acts as an inhibitory molecule to restrict T-cell responses. ... Leach, D. R.; Krummel, M. F.; Allison, J. P. (March 22, 1996). "Enhancement of Antitumor Immunity by CTLA-4 Blockade". Science ...
... with B7 on T cells Downregulation of CD80/CD86 costimultory molecules on antigen presenting cells upon interaction with CTLA-4 ... tumor antigens, alloantigens, and self-antigens in inflamed tissue. Immune recognition of non-self-antigens typically ... Self-antigens are present due to endogenous expression, importation of antigen from peripheral sites via circulating blood, and ... Upon exposure to a foreign antigen, either the antigen is eliminated by the standard immune response (resistance), or the ...
In order for T cells to be activated and attack an antigen, that antigen must be presented to the T cell by an antigen- ... Abatacept consists of a fusion protein of the extracellular domain of CTLA-4 and human IgG1, binds to the B7 protein on the APC ... Abatacept prevents antigen-presenting cells (APCs) from delivering the co-stimulatory signal. This prevents the T cells from ... "ABATACEPT & BELATACEPT: the CTLA-4-Igs". Healthvalue.net. Retrieved 2007-05-25. Dall'Era M, Davis J (2004). "CTLA4Ig: a novel ...
Hirohashi N, Nakao M, Kubo K, Yamada A, Shichijo S, Hara A, Sagawa K, Itoh K (Dec 1993). "A novel antigen (H47 Ag) on human ... CTLA-4) on cytokine production by antigen-stimulated human T cells". Journal of Immunology. 168 (1): 207-15. doi:10.4049/ ... The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a ... 3.0.CO;2-4. PMID 9933109. Chapman TL, Heikeman AP, Bjorkman PJ (Nov 1999). "The inhibitory receptor LIR-1 uses a common binding ...
... blocks the binding of the antigen-presenting cell ligands B7.1 and B7.2 to CTLA-4, resulting in inhibition of B7- ... Mechanism of Pathway: CTLA-4 Inhibition[permanent dead link] Antoni Ribas (28 June 2012). "Tumor immunotherapy directed at PD-1 ... Tremelimumab binds to the protein CTLA-4, which is expressed on the surface of activated T lymphocytes and inhibits the killing ... Unlike Ipilimumab (another fully human anti-CTLA-4 monoclonal antibody), which is an IgG1 isotype, tremelimumab is an IgG2 ...
... foreign transplants and cancer cell neo-antigens. Rudd also uncovered signaling mechanisms by which co-receptors CD28, CTLA-4 ... By showing that CTLA-4 activates T-cell motility and migration, he proposed the 'reverse-stop signal model' to account for CTLA ... 2006) Reversal of the TCR stop signal by CTLA-4. Science. 313,1972-5. Wei B, Han L, Abbink TEM, Elisabetta G, Lim D, Thaker R, ... 1989) The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. Proc. ...
TNFRSF25 is activated by a monogamous ligand, known as TL1A (TNFSF15), which is rapidly upregulated in antigen presenting cells ... effects as coinhibitory receptor blockade targeting molecules such as CTLA-4 and PD-1. GRCh38: Ensembl release 89: ... Similarly, because TNFRSF25 activation is antigen dependent, costimulation of TNFRSF25 together with an autoantigen or with a ... This receptor is expressed preferentially by activated and antigen-experienced T lymphocytes. TNFRSF25 is also highly expressed ...
A major antigen in these is a protein called Bet V I. Olive pollen is most predominant in Mediterranean regions. Hay fever in ... On the other hand, CTLA-4 is an immune-checkpoint protein that helps mediate and control the body's immune response to prevent ... There have been two SNPs in CTLA-4 that were found to be significantly associated with childhood allergic rhinitis. Both SNPs ... 20 (5). Song SH, Wang XQ, Shen Y, Hong SL, Ke, X. "Association between PTPN22/CTLA-4 Gene Polymorphism and Allergic Rhinitis ...
... antigen-specific) Treg suppressive activity. Combination therapies are also ongoing involving LAG-3 antibodies and CTLA-4 or PD ... A new ligand for human leukocyte antigen class II antigens". The Journal of Experimental Medicine. 176 (2): 327-37. doi:10.1084 ... A new ligand for human leukocyte antigen class II antigens". The Journal of Experimental Medicine. 176 (2): 327-37. doi:10.1084 ... An initial characterization of the LAG-3 protein was reported in 1992 showing that it was a ligand for MHC class II antigens ...
Binding of the B7 of APC to CTLA-4 of T-cells causes inhibition of the activity of T-cells. There are two major types of B7 ... This is also called "Signal 1" and its main purpose is to guarantee antigen specificity of the T cell activation. However, MHC ... The B7-CTLA-4 binding suppresses T cell activation. The balance between the opposing signals generated by B7-CD28 and B7-CLTA-4 ... CTLA-4-knockout mice are unable to stop immune responses, and develop a fatal massive lymphocyte proliferation. Apart from B7-1 ...
Examples of such a molecule are cytotoxic T-lymphocyte antigen 4 (CTLA-4 or CD152), which is an inhibitory receptor found on ... particularly against T cells that are specific for tumor antigens. Therefore, the strategy in using immunological checkpoints ...
Inhibitory signals to PD-1 and CTLA-4 are immune checkpoints, and binding of these inhibitory receptors by their ligands ... and cytotoxic T-lymphocyte antigen 4 (CTLA-4), respectively, on T cells. ... 25 (4): 656-666. doi:10.1038/s41591-019-0374-x. PMC 7175920. PMID 30833750. Martinez FO, Gordon S (3 March 2014). "The M1 and ... 36 (4): 229-39. doi:10.1016/j.it.2015.02.004. PMID 25770924. Qian BZ, Pollard JW (April 2010). "Macrophage diversity enhances ...
Th3 cells can be activated by TCR stimulation after the recognition of an antigen or induced from CD4+ T lymphocytes by TGF-β ... CTLA-4), which is constitutively expressed on naturally arising Treg cells, it is possible that TGF-β production from Treg ... Th3 cells are involved in mucosal immunity and protecting mucosal surfaces in the gut from non-pathogenic non-self antigens. ... Additionally, since TGF-β production was induced by cytotoxic T-lymphocyte antigen 4 ( ...
March 2017). "Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy". The Journal of Clinical ... as shown by an increase in response with blockade to PD-1 and CTLA-4 via monoclonal antibodies as compared to the blockade of a ... Finally, inhibition of A2AR, either through pharmacologic or genetic targeting, in chimeric antigen receptor (CAR) T-cells ... especially with the therapeutic success of the blockade of other checkpoint pathways such as PD-1 and CTLA-4. GRCh38: Ensembl ...
These tumor antigens are either TSA (Tumor-specific antigen) or TAA (Tumor-associated antigen). Tumor-specific antigens (TSA) ... Brunner-Weinzierl MC, Rudd CE (2018-11-27). "CTLA-4 and PD-1 Control of T-Cell Motility and Migration: Implications for Tumor ... Oncofetal antigens are tumor-associated antigens expressed by embryonic cells and by tumors. Examples of oncofetal antigens are ... role of antigen load, antigen-presenting cells, and cytokines". Journal of Immunology. 163 (1): 130-6. PMID 10384108. Scheffer ...
It acts as an "off" switch when bound to CD80 or CD86 on the surface of antigen-presenting cells. The CTLA-4 protein is encoded ... on antigen-presenting cells. CTLA-4 binds CD80 and CD86 with greater affinity and avidity than CD28 thus enabling it to ... needed for firm contact between T cells and antigen-presenting cells (APCs). However, those studies compared CTLA-4 positive ... CTLA-4 was first identified in 1991 as a second receptor for the T cell costimulation ligand B7 (Bashyam, 2007). In November ...
CD antigens". Immunobiology (5 ed.). New York: Garland. ISBN 978-0-8153-3642-6. Vivier E, Morin P, O'Brien C, Druker B, ... Sharma N, Vacher J, Allison JP (May 2019). "TLR1/2 ligand enhances antitumor efficacy of CTLA-4 blockade by increasing ... CD16+Antigens at the US National Library of Medicine Medical Subject Headings (MeSH). ... Elghetany MT (March 2002). "Surface antigen changes during normal neutrophilic development: a critical review". Blood Cells, ...
DCs are also the only cell type which can activate naïve T cells and induce antigen-specific immune responses. Therefore, their ... "Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4". Nature Immunology. 6 (3): 280-6. doi: ... Tolerogenic effect has been demonstrated also by over-expression of Jagged-1 on DCs which in turn induced antigen specific T ... Mills KH, McGuirk P (April 2004). "Antigen-specific regulatory T cells--their induction and role in infection". Seminars in ...
Antigen Antigenicity Immunogen Superantigen Allergen Hapten Epitope Linear Conformational Mimotope Tumor antigen Antigen- ... expressed by T Cells CTLA-4 (CD152) PD-1 (CD279) Immune disorder Type 1 hypersensitivity / Allergy / Atopy Foreign (Allergen) ... T cells Antigen receptor - T cell receptor (TCR) Subunits - [email protected] / [email protected] / [email protected] / [email protected] Co-receptors CD8 (CD8α / CD8β) CD4 ... CD18 Macrophage-1 antigen (CR3) - Heterodimer: CD11b / CD18 Integrin alphaXbeta2 (CR4) - Heterodimer: CD11c / CD18 Very late ...
A number of approaches have been considered to amplify T cell mediated immune responses(e.g. IL-2, CTLA-4, IL-7, CD137), and ... tumor-associated antigens, or whole tumor cells, can induce specific T-cell mediated immune responses. ... Blood 2008;111(4):2112-21. Rapoport AP, Stadtmauer EA, Aqui N, et al. Restoration of immunity in lymphopenic individuals with ... Int J Cancer 2001;94(4):531-9. Rousseau RF, Biagi E, Dutour A, et al. Immunotherapy of high-risk acute leukemia with a ...
Antigen-naïve T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen ... CTLA-4, T cell membrane protein-3 (TIM3), and lymphocyte activation gene 3 protein (LAG3).[59][60] Soluble molecules such as ... T cell exhaustion can be triggered by several factors like persistent antigen exposure and lack of CD4 T cell help.[57] Antigen ... Antigen discrimination[edit]. A unique feature of T cells is their ability to discriminate between healthy and abnormal (e.g. ...
MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. Proceedings of the National ... CTLA-4在活化T细胞表面的上调,对共激活受体有竞争性抑制作用,可以避免活化T细胞的过度活化。活化T细胞的表面糖基化情况也有改变[32]。 ... An induced rebinding model of antigen discrimination. Trends Immunol. 2014, 35 (4): 153-8. PMC 3989030. PMID 24636916. doi: ...
BLyS (Belimumab) • CTLA-4 (Ipilimumab, Tremelimumab) • CAT (Bertilimumab, Lerdelimumab, Metelimumab) • Integrin (Natalizumab) • ... Induction of Potent and Long-Lasting T-Cell Responses against Cancer Antigens". Cancer Research 62: 1477-1480. ... Na primer, za ženske polne hormone je poznato da stimulišu i adaptivni[4] i urođeni imunski odgovor.[5] Neke autoimune bolesti ... "A divalent major histocompatibility complex/IgG1 fusion protein induces antigen-specific T cell activation in vitro and in ...
CTLA-4 - białko to wiąże się z cząsteczkami CD80 i CD86 na komórkach prezentujących antygen. Skutkuje to pobraniem tych ... Antigen-specific peripheral shaping of the natural regulatory T cell population. „J Exp Med". 205 (13), s. 3105-3117, grudzień ... TGF-beta requires CTLA-4 early after T cell activation to induce FoxP3 and generate adaptive CD4+CD25+ regulatory cells. „J ... De novo production of antigen-specific suppressor cells in vivo. „Nat Protoc". 1 (2), s. 653-661, 2006. PMID: 17802642. ...
"Guiding the selection of human antibodies from phage display repertoires to a single epitope of an antigen". Bio/Technology. 12 ... Retrieved 4 February 2014.. This article incorporates text from this source, which is in the public domain. ... 2 (4): 375-7. PMID 12884458.. *^ Maxwell LJ, Zochling J, Boonen A, Singh JA, Veras MM, Tanjong Ghogomu E, et al. (18 April 2015 ... "Retrieved 4 February 2014.. *^ "FDA approves Humira to treat ulcerative colitis" (Press release). U.S. Food and Drug ...
T细胞上的受体CTLA-4(英语:CTLA-4)会抑制免疫系统,有些癌細胞便會依此機制來逃脫免疫系統的偵查。伊匹单抗(英语:Ipilimumab)(Ipilimumab)會抑制CTLA-4,藉此來阻断其信号传导,減少癌細胞逃脫的機會,FDA已批准其用于治 ... 嵌合抗原受體T細胞免
BLyS (Belimumab) • CTLA-4 (Ipilimumab, Tremelimumab) • CAT (Bertilimumab, Lerdelimumab, Metelimumab) • Integrin (Natalizumab ... ćelije bile identifikovane kao najpotentniji proizvođači tipa I interferona u odgovoru na antigen, i bile su nazvani prirodne ...
BLyS (Belimumab) • CTLA-4 (Ipilimumab, Tremelimumab) • CAT (Bertilimumab, Lerdelimumab, Metelimumab) • Integrin (Natalizumab ... Nakon presađivanja (transplantacije) organa, telo skoro uvek „odbaci" novi organ usled razlike ljudskih leukocit antigen ...
BLyS (Belimumab) • CTLA-4 (Ipilimumab, Tremelimumab) • CAT (Bertilimumab, Lerdelimumab, Metelimumab) • Integrin (Natalizumab) ... ćelije bile identifikovane kao najpotentniji proizvođači tipa I interferona u odgovoru na antigen, i bile su nazvani prirodne ... proinflamatorni citokin (IL-1, TNF-alfa) • Th1 (INF-gama i TNF-beta) • Th2 (IL-4, IL-5, IL-6, IL-10, IL-13) • Th17 (IL-17,IL-22 ... 4-1BB ligand • Faktor aktivacije B-ćelija • FAS ligand • Limfotoksin • OX40L • RANKL • TRAIL ...
Antigen-naïve T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen ... CTLA-4, T cell membrane protein-3 (TIM3), and lymphocyte activation gene 3 protein (LAG3).[53][54] Soluble molecules such as ... T cell exhaustion can be triggered by several factors like persistent antigen exposure and lack of CD4 T cell help.[51] Antigen ... Antigen discriminationEdit. A unique feature of T cells is their ability to discriminate between healthy and abnormal (e.g. ...
Past this period CD3 blocks the TCR-antigen binding and causes conformational change or the removal of the entire TCR3/CD3 ... The IL-2a (CD25, T-cell activation antigen, TAC) is expressed only by the already-activated T lymphocytes. Therefore, it is of ... The antilymphocyte (ALG) and antithymocyte antigens (ATG) are being used. They are part of the steroid-resistant acute ... Monoclonal antibodies are directed towards exactly defined antigens. Therefore, they cause fewer side-effects. Especially ...
immunoglobin CTLA-4 fusion protein T-cell deactivation adalimumab Humira rheumatoid arthritis, ankylosing spondylitis, ... Vaccines (Hepatitis B surface antigen). *Monoclonal antibodies (Various). *Additional products (tumour necrosis factor, ... 18 (4): 369-379. doi:10.1080/14712598.2018.1421169. PMID 29285958.. *^ a b Nick C (2012). "The US Biosimilars Act: Challenges ... 29 (4): 310-2. doi:10.1038/nbt.1839. PMID 21478841.. *^ Lamanna WC, Holzmann J, Cohen HP, Guo X, Schweigler M, Stangler T, ...
Downregulation of CD80/CD86 costimultory molecules on antigen presenting cells upon interaction with CTLA-4 or lymphocyte ... Self-antigens are present due to endogenous expression, importation of antigen from peripheral sites via circulating blood, and ... Upon exposure to a foreign antigen, either the antigen is eliminated by the standard immune response (resistance), or the ... nTreg cells are specific, modestly, for self-antigen while iTreg cells recognize allergens, commensal bacteria, tumor antigens ...
BLyS (Belimumab) • CTLA-4 (Ipilimumab, Tremelimumab) • CAT (Bertilimumab, Lerdelimumab, Metelimumab) • Integrin (Natalizumab) ... su naspramni jedan drugom i formiraju antigen-vezujuće mesto, tako da molekul antitela sadrži dva antigen-vezujuća mesta. ... Funkcionira uglavnom kao antigen receptor na B-limfocitima koji nisu bili izloženi antigenima. Dokazano je da aktivira bazofile ... i spremnim da odgovore na antigen. Aktivacija B ćelija prati angažman ćelijski vezanih molekula antitijela sa antigenom, ...
HMB-45 is a monoclonal antibody that reacts against an antigen present in melanocytic tumors such as melanomas. It is used in ... Immune check point inhibitors include anti-CTLA-4 monoclonal antibodies (ipilimumab and tremelimumab), toll-like receptor (TLR ... 18 (4): 351-357. doi:10.1080/14737167.2018.1467270. PMID 29681201.. *^ a b c d West HJ (April 2015). "JAMA Oncology Patient ... 129 (4): 56. doi:10.1002/14651858.CD004835.pub2. PMID 19821334.. *^ a b Mohs FE, Mikhail GR (January 1991). Mohs micrographic ...
This phenotype is similar to those that lack expression of CTLA-4, TGF-β, human disease IPEX, or deletion of the Foxp3 gene in ... tolerance induction to self antigen. • regulation of transcription, DNA-templated. • negative regulation of sequence-specific ... 4 (4): 330-6. doi:10.1038/ni904. PMID 12612578.. *^ a b Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY ... negative regulation of interleukin-4 production. • negative regulation of interleukin-10 production. • negative regulation of ...
Tumor markers including alphafetoprotein (AFP),[47] Beta Human Chorionic Gonadotropin (HCG),[47] Carcinoembionic Antigen (CEA), ... Treatment options include surgery, radiation, targeted therapy (BRAF & MEK inhibitors), Immunotherapy (CTLA 4 & PD 1 inhibitors ... 54 (4): 401-410. ISSN 1824-4785. PMID 20823808.. *^ a b Bassetto, M. A.; Franceschi, T.; Lenotti, M.; Parise, G.; Pancheri, F ... 68 (4): 1068. doi:10.1086/319526. ISSN 0002-9297. PMC 1275628 .. *^ Breen, Matthew (2009-08-01). "Update on genomics in ...
Goodpasture-antigen-binding protein kinase (EC 2.7.11.9). *-. IκB kinase (EC 2.7.11.10). *CHUK ... 16 (4): 525-37. doi:10.1093/annonc/mdi113. PMID 15728109.. *^ a b c d e f g h i j k l m n Zaytseva, Yekaterina Y.; Valentino, ... 121 (4): 1231-41. doi:10.1172/JCI44145. PMC 3069769. PMID 21490404.. *^ a b c d Tanneeru, Karunakar; Guruprasad, Lalitha (2011 ... However they have improved hydrophilicity and can be used for oral and intravenous administration.[4] In 2012 National Cancer ...
Tr1 cells regulate tolerance towards antigens of any origin. Tr1 cells are self or non-self antigen specific and their key role ... Type 1 regulatory T cells poses inhibitory receptor CTLA-4 through which they exert suppressor function. Metabolic disruption: ... and enhances the antigen-specific T-cell response which is necessary for Tr1 cells antigen specificity. CD49b belongs to the ... IL-10 indirectly downregulates MHC II molecules and co-stimulatory molecules on antigen-presenting cells (APC) and force them ...
Genetic basis for clinical response to CTLA-4 blockade in melanoma ". The New England Journal of Medicine. 371(23): 2189-2199. ... 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 ...
Lakins MA, Ghorani E, Munir H, Martins CP, Shields JD (2018). "Cancer-associated fibroblasts induce antigen-specific deletion ... mechanism by which tumors can suppress T cell infiltration similar to inhibitory immune checkpoints such as PD-1 and CTLA-4. ... pathway are the two main mechanisms by which cytotoxic T lymphocytes induce cell death in cells expressing foreign antigens. ...
A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy. Cell Res. 2018;28(4):416-432. "2018 Archives , University ... His interest in this question was kindled when he made the observation that viral activation of host antigen-presenting cells ... induce co-stimulatory activity in antigen-presenting cells, and proposed that microbial induction of co-stimulatory molecules ... 4] Liu Y, Chen GY, Zheng P.CD24-Siglec G/10 discriminates danger- from pathogen-associated molecular patterns. Trends Immunol. ...
Two of these inhibitory proteins that have been studied recently are CTLA-4 and PD1, and drugs targeting these proteins are in ... Adoptive immunotherapy seeks to expand a population of the body's T-cells that will recognize a specific tumor antigen. T-cells ... They can also include the administration of laboratory-produced antibodies specific to tumor antigens to create or boost an ... Vaccines can deliver various tumor-associated factors (tumor antigens) to the immune system, resulting in a natural antibody ...
In turn, clonal expansion of antigen-specific CD8+ T cells and/or CD4+ helper cells is propagated. The binding of PD-L1 to the ... is intermediate between its affinities for CD28 and CTLA-4 (4.0µM and 400nM, respectively). The related molecule PD-L2 has no ... Normally the adaptive immune system reacts to antigens that are associated with immune system activation by exogenous or ... monocytogenes antigen-specific CD8 T cells (but not CD4 T cells). This evidence suggests that PD-L1 acts as a positive ...
... has been shown to interact with: AXIN1, CTLA-4, PPP2CA, PPP2R1A, PPP2R1B, and PPP2R5C GRCh38: Ensembl release 89: ... "Binding specificity of protein phosphatase 2A core enzyme for regulatory B subunits and T antigens". Journal of Virology. 73 (1 ... "Inhibition of CTLA-4 function by the regulatory subunit of serine/threonine phosphatase 2A". Journal of Immunology. 168 (10): ... 121 (4): 270-86. PMID 15817944. Zolnierowicz S, Van Hoof C, Andjelković N, Cron P, Stevens I, Merlevede W, Goris J, Hemmings BA ...
CTLA-4 is down-regulated following OX40 engagement in vivo and the OX40-specific TRAF3 DN defect was partially overcome by CTLA ... is also not expressed on resting antigen presenting cells, but is following their activation. Expression of OX40 is dependent ... TRAF3 may be linked to OX40-mediated memory T cell expansion and survival, and point to the down-regulation of CTLA-4 as a ... Arch RH, Thompson CB (January 1998). "4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor ...
Recent research has focused on a defect at the CTLA-4 gene which, coupled with other factors, may result in autoimmunity ... Hepatitis Weekley, Autoimmune Diseases, "Cytotoxic Antigen Induces Hypophysitis in Cancer Patients," 2006-1-9; see also, Weston ... "Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic ... 152 (4): 589-96. doi:10.1530/eje.1.01873. PMID 15817915. Biller BM, Samuels MH, Zagar A, Cook DM, Arafah BM, Bonert V, Stavrou ...
Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis.. Agarwal K1, ... The CTLA-4 G allele is more common in patients with type 1 autoimmune hepatitis and may represent a second susceptibility ... To determine the frequency and significance of the exon 1 adenine (A)-guanine (G) base-exchange polymorphism for CTLA-4 in ... The gene encoding cytotoxic T-lymphocyte antigen-4 (CTLA-4) on chromosome 2q33 may also influence autoimmunity. ...
Vaccination induced a measurable antigen-specific T-cell response that increased following CTLA-4 blockade, potentially " ... CTLA-4 blockade increases antigen-specific CD8(+) T cells in prevaccinated patients with melanoma: three cases.. Yuan J1, ... Tumor escape may be related to antigen loss or lack of MHC expression necessary for immune activity. These results in a limited ... CTLA-4 blockade increases antigen-specific CD8+ T-cells in prevaccinated patients with melanoma: three cases ...
antigen-presenting cell;. ELISPOT,. enzyme-linked immunospot assay;. CTLA-4,. cytotoxic T lymphocyte antigen-4. ... Most of the CD4+ T cells in the AND TCR+ CTLA-4+ mice had a naive phenotype and were CD44lo, MEL14hi, CD45RBhi (Fig. 1B). In ... The CTLA-4+/− mice were crossed to an MHC class II-restricted TCR (AND TCR) (Vβ3Vα11) transgenic mouse strain that is selected ... The expected skewing toward CD4+ T cells was observed in the AND TCR+ CTLA-4+/+ or CTLA-4+/− (AND TCR+ CTLA-4+) mice, and ,90% ...
Thus, effective vaccination against tumor antigens could in fact provide an important partner to CTLA-4 and PD-1/PD-L1 blockade ... TILs in response to peptide presented by antigen-presenting cells. Thus, our work clearly demonstrated that double PD-1/CTLA-4 ... CTLA-4 blockade alone was able to enhance the proliferation only of PD-1+CTLA-4+ CD8+ TILs and had no effect on CTLA-4− cells. ... PD-L1/CTLA-4 blockade also induced higher numbers of TILs and a higher ratio of CD8+ to Treg cells. Clinical evidence to date ...
... we designed antigen-specific inhibitory chimeric antigen receptors (iCARs) to preemptively constrain T cell responses. We ... The initial effect of the iCAR is temporary, thus enabling T cells to function upon a subsequent encounter with the antigen ... PD-1- and CTLA-4-Based Inhibitory Chimeric Antigen Receptors (iCARs) Divert Off-Target Immunotherapy Responses ... PD-1- and CTLA-4-Based Inhibitory Chimeric Antigen Receptors (iCARs) Divert Off-Target Immunotherapy Responses ...
The discovery of cytotoxic T-lymphocyte antigen-4 (CTLA-4) … ... Targeting CTLA-4 as an anticancer strategy: Following proof-of- ... The discovery of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and its role as a key negative regulator for T cells has prompted ... Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4): a novel strategy for the treatment of melanoma and other malignancies ... Signal 1 requires tumor-associated antigen recognition by the T-cell receptor, while signal 2 occurs through binding of CD80 or ...
Activation B7-1 Antigen or CTLA 4 Counter Receptor B7. ... T Lymphocyte Activation Antigen CD80 (Activation B7-1 Antigen ... T Lymphocyte Activation Antigen CD80 (Activation B7-1 Antigen or CTLA 4 Counter Receptor B7.1 or CD80) - Pipeline Review, H2 ... T Lymphocyte Activation Antigen CD80 (Activation B7-1 Antigen or CTLA 4 Counter Receptor B7.1 or CD80) - Cluster of ... T Lymphocyte Activation Antigen CD80 (Activation B7-1 Antigen or CTLA 4 Counter Receptor B7.1 or CD80) pipeline Target ...
The NY-ESO-1 antigen-specific CD4+ T cell response induced by CTLA-4 blockade revealed a polyfunctional response pattern of MIP ... Polyfunctional NY-ESO-1 antigen-specific T cells secreted higher levels of IFN-γ after anti-CTLA-4 antibody treatment. (A) IFN- ... 2006) Tumor antigen expression in melanoma varies according to antigen and stage. Clin Cancer Res 12:764-771. ... NY-ESO-1 antigen specific response in patients treated with anti-CTLA-4 antibody ...
... plays a critical role in downregulation of antigen-activated immune response and polymorphisms at the CTLA-4 gene have been ... that is believed to control the processing and production of soluble CTLA-4 (sCTLA-4). We therefore determined sCTLA-4 protein ... Higher levels of sCTLA-4 were observed in T1D (2.24 ng/ml) and AbP (mean = 2.17 ng/ml) subjects compared to AbN controls (mean ... Consistent with the higher serum sCTLA-4 levels observed in other autoimmune diseases, our results suggest that sCTLA-4 may be ...
Compare Antigen NY-CO-13 ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, reviews, and ... DuoSet CTLA-4 ELISA Our laboratory focuses on effects of aryl hydrocarbon receptor (AhR) activation in dendritic cells. ... ... Antigen NY-CO-13 ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a well-established antibody-based tool for ... Your search returned 158 Antigen NY-CO-13 ELISA ELISA Kit across 10 suppliers. ...
Compare B melanoma antigen family member 3 ELISA Kits from leading suppliers on Biocompare. View specifications, prices, ... DuoSet CTLA-4 ELISA Our laboratory focuses on effects of aryl hydrocarbon receptor (AhR) activation in dendritic cells. ... ... B melanoma antigen family member 3 ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a well-established antibody- ... Your search returned 2 B melanoma antigen family member 3 ELISA ELISA Kit across 1 supplier. ...
It remains clear, however, that CD28 and cytotoxic T lymphocyte antigen 4 (CTLA-4) are the critical costimulatory rec … ... CTLA-4: new insights into its biological function and use in tumor immunotherapy Nat Immunol. 2002 Jul;3(7):611-8. doi: 10.1038 ... We summarize here recent findings that suggest a previously unrecognized role for CTLA-4 in the regulation of T cell responses ... We also describe preclinical and clinical results that indicate manipulation of CTLA-4 has considerable promise as a strategy ...
Diversity of antigen-specific responses induced in vivo with CTLA-4 blockade in prostate cancer patients. J. Immunol. 189, 3759 ... We assessed HLA-A*0201+ patients to a panel of tetramers for self-antigens because these antigen-specific T cells would be ... promoting a diverse population of antigen-specific T cells (24). CTLA-4 blockade could reduce the diversity of responding T ... tumor-specific T cell clones that have been primed by APC with tumor antigens but are attenuated by subsequent CTLA-4 ...
The immunocytokine L19-IL2 eradicates cancer when used in combination with CTLA-4 blockade or with L19-TNF. J Invest Dermatol ... Cytotoxic T-lymphocyte antigen 4. DCR. Disease control rate. EDB. Extra-domain B ... Oncologist 11(4):397-408. doi: 10.1634/theoncologist.11-4-397 PubMedCrossRefGoogle Scholar ... 4.. Smith FO, Downey SG, Klapper JA, Yang JC, Sherry RM, Royal RE, Kammula US, Hughes MS, Restifo NP, Levy CL, White DE, ...
Cytotoxic T-lymphocyte antigen 4Imported. Automatic assertion inferred from database entriesi ... CTLA-4 proteinImported. ,p>Information which has been imported from another database using automatic procedures.,/p> ,p>,a href ... tr,Q28090,Q28090_BOVIN CTLA-4 protein OS=Bos taurus OX=9913 GN=CTLA4 PE=1 SV=1 ... Cytotoxic T-lymphocyte-associated protein 4Imported. Automatic assertion inferred from database entriesi ...
Rigid-body Ligand Recognition Drives Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) Receptor Triggering ... Rigid-body Ligand Recognition Drives Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) Receptor Triggering ... Rigid-body Ligand Recognition Drives Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) Receptor Triggering ...
Quantitative assay of protein antigen, immunoglobulin G, by means of enzyme-labelled antigen and antibody-coated tubes. Biochim ... In a study of therapeutic effects of ipilimumab (monoclonal antibody targeting CTLA-4), an increased secretion of IL-1β, IL-2, ... Van Weemen, B.K.; Schuurs, A.H.W.M. Immunoassay using antigen-enzyme conjugates. FEBS Lett. 1971, 15, 232-236. [Google Scholar ... Antigen is captured by an antibody immobilized on magnetic microbeads and by addition of biotinylated detection antibody and ...
E. J. Lipson and C. G. Drake, "Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma," Clinical Cancer Research, vol. 17 ... Nanopores have great potential for detecting biomolecules such as DNA, antigens, ions, and drugs [30]. Nanopores may consist of ... The checkpoint regulators CTLA-4 and PD-1 expressed in immune cells were successfully targeted for immunotherapies: in ... A cantilever microassay for PSA detection consists of laser measurement of bend deflection caused by antibody-antigen specific ...
Carbohydrate Antigen 19-9. CI. confidence interval. CSCs. Cancer stem cells. CTLA-4. cytotoxic T-lymphocyte-associated antigen ... Induction of T-cell Immunity Overcomes Complete Resistance to PD-1 and CTLA-4 Blockade and Improves Survival in Pancreatic ... Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J. ... CTLA-4) or programmed death 1 (PD-1)/programmed death receptor ligand-1 (PD-L1) blocking antibodies to release the brakes from ...
Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and anti-CTLA-4 therapies in Cancer: mechanisms of action, efficacy, and ... as OVs should make the TME significantly more immunogenic due to inflammation and the presence of viral antigens. Such a ... In this context, the combination of different checkpoint inhibitors (anti-CTLA-4 and anti-PD1 Abs) yielded better results in ... CTLA-4), Programmed Death-1 (PD-1), or its ligands PDL-1 and PDL-2 [15]. Anti-CTLA-4 humanized antibodies, as ipilimumab, were ...
Investigating the role of CTLA-4 either using anti-CTLA-4 mAb or by generating chimeras using DO11.10xCTLA-4(-/-) mice as ... and lamina propria following primary exposure to antigen. Using this model we have demonstrated initial activation in all three ... indicating that secretion of this cytokine by antigen-specific cells is not required. ... using transfer of DO11.10 TCR-transgenic bone marrow into irradiated recipients in which it has been possible to track antigen- ...
Mechanism of vaccine antigen-specific and non-vaccine antigen-specific Teff recruitment to the inflamed vaccination site. Left ... We previously reported (13) that vaccination with gp100 peptide in IFA creates a persisting antigen depot that primes antigen- ... Since leukocyte function-associated antigen 1 (LFA-1, also known as αLβ2) and very late antigen 4 (VLA-4, also known as α4β7) ... antigen-specific and cognate (gp100) antigen-specific non-pmel-1 Teffs did not reach the tumor and instead colocalized with ...
Chimeric antigen receptor T-cell therapy at any time. *Organ transplantation, including allogeneic or autologous stem-cell ... Vopratelimab and a CTLA-4 Inhibitor in PD-1/PD-L1 Inhibitor Experienced Subjects With NSCLC or Urothelial Cancer (EMERGE). The ... Anti-CTLA-4. Ipilimumab. EMERGE. Immunotherapy. Immuno-Oncology. Cancer. Non-small Cell Lung Cancer. Urothelial Cancer. ... Phase 2 Multicenter Trial of ICOS Agonist Monoclonal Antibody (mAb) JTX -2011 and a CTLA-4 Inhibitor in PD-1/PD-L1 Inhibitor ...
Goat Polyclonal Anti-CTLA-4 Antibody [Unconjugated]. Validated: WB, Flow, CyTOF-ready, ICC/IF. Tested Reactivity: Human. 100% ... Cold acetone for 15 min at room temperature, PBS 5 for min at room temperature, No antigen retrieval,. ... CTLA-4 Antibody [Unconjugated] Summary. Immunogen. S. frugiperda insect ovarian cell line Sf 21-derived recombinant human CTLA- ... Check out the latest blog posts on CTLA-4.. Thomson Reuters Predicts 2016 Nobel Prize Winners. Here at Bio-Techne we always ...
We show that the presence and severity of TAO are associated with an allele of the cytotoxic T lymphocyte antigen-4-gene. ... Abatacept, Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Antigens, CD, Antigens, Differentiation, CTLA-4 Antigen, Child ... Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism confers susceptibility to thyroid associated orbitopathy. ... We show that the presence and severity of TAO are associated with an allele of the cytotoxic T lymphocyte antigen-4-gene. ...
Blocking CTLA-4 allows T cells to attack and destroy tumors.. While ipilimumab is no longer the frontline choice for treating ... Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) blocker. Treatment overview. Approved by the FDA in 2011 for patients with stage IV ... Ipilimumab targets CTLA-4, a protein on the T cell that functions as a "brake" to regulate immune system activation. ...
0/Antigens, CD; 0/Antigens, Differentiation; 0/cytotoxic T-lymphocyte antigen 4 ... Antigens, CD. Antigens, Differentiation / genetics*. European Continental Ancestry Group / genetics. Female. Genetic ... A49G polymorphism in position 49 of exon-1 of the CTLA-4 gene was studied by the polymerase chain reaction-single-strand ... In addition, the critical role of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) molecule in maintaining self-tolerance has been ...
CTLA-4+) T reg cells (30), recommending that CTLA-4 on T reg cells is pertinent for initiating and/or preserving regulation ... Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a crucial role in negatively regulating T cell responses and has also been ... It is a human NK cell associated antigen. CD16 is a low affinity receptor for IgG which functions in phagocytosis and ADCC ... Outcomes CTLA-4Csufficient blastocyst and BM-derived cells stably regulate T cells in vivo mice develop substantial ...
Conclusion Vaccination induced a measurable antigen-specific T-cell response which increased following CTLA-4 blockade, ... Background Anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibodies, such as ipilimumab, have generated. * Post author By ... Tumor escape may be related to antigen loss or lack of MHC expression necessary for immune activity. These results in a limited ... Antigen Deforolimus detection was performed by a color reaction with 3,3-diaminobenzidine (DAB + chromogen, DakoCytomation, ...
Antigens, Neoplasm/immunology , Antigens, Neoplasm/metabolism , Cancer Vaccines/immunology , CTLA-4 Antigen/genetics , CTLA-4 ... Animals , Male , Mice , Antigens, Neoplasm/therapeutic use , Cancer Vaccines/therapeutic use , CTLA-4 Antigen/therapeutic use ... Consequently, we constructed a DNA vaccine containing the PSCA and the CTLA-4 gene. Vaccination with the CTLA4-fused DNA not ... Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for ...
  • Conversely, recent studies indicate that CD28 homologue CTLA-4 inhibits T cell responses ( 4 ). (pnas.org)
  • Further, we have proposed a two-signal model for T cell activation in which T cell responses are regulated by the dynamic integration of TCR, CD28, and CTLA-4 signals ( 14 ). (pnas.org)
  • Signal 1 requires tumor-associated antigen recognition by the T-cell receptor, while signal 2 occurs through binding of CD80 or CD86 (B7.1 of 2) on the antigen presenting cell (APC) with CD28 on the T cell. (nih.gov)
  • CTLA-4 is of primary importance in maintaining immune homeostasis by downregulating T cell signaling to inhibit the CD28-B7 costimulatory pathway, limiting T cell responses and contributing to tolerance to self antigens ( , 5 , , 6 ). (pnas.org)
  • It remains clear, however, that CD28 and cytotoxic T lymphocyte antigen 4 (CTLA-4) are the critical costimulatory receptors that determine the early outcome of stimulation through the T cell antigen receptor (TCR). (nih.gov)
  • Details of how the T cell integrates TCR stimulation with the costimulatory signals of CD28 and the inhibitory signals of CTLA-4 remain to be established, but unique features of the cell biology of CTLA-4 provide important insights into its function. (nih.gov)
  • CTLA-4 binds to B7 ligands expressed on antigen-presenting cells (APCs) with higher affinity than the costimulatory molecule CD28, and both its gene and surface expression are induced during T cell activation upon APC interaction ( 1 ). (sciencemag.org)
  • CTLA-4 and CD28, together with their ligands B7-1 and B7-2, constitute one of the dominant costimulatory pathways that regulate T- and B-cell responses. (novusbio.com)
  • CTLA-4 and CD28 are structurally homologous molecules that are members of the immunoglobulin (Ig) gene superfamily. (novusbio.com)
  • CTLA-4 and CD28 are both expressed on the cell surface as disulfide-linked homodimers or as monomers. (novusbio.com)
  • The T cell receptor CTL-associated antigen 4 (CTLA-4) is recognized as a critical inhibitory regulator of the early stages of T cell expansion, opposing the actions of CD28-mediated costimulation. (rupress.org)
  • A cell autonomous mechanism of action for CTLA-4, with CTLA-4 acting when expressed in cis of CD28, is supported by several lines of data. (rupress.org)
  • CTLA-4, a protein with structural similarities to CD28, is expressed on activated T cells at low level and binds the B7 family members, CD80 (B7-1) and CD86 (B7-2), with higher affinity than CD28 does. (thermofisher.com)
  • CTLA-4 and CD28 appear to deliver opposing signals to T cells: while CD28 is a potent costimulator, CTLA-4 restricts the progression of T cells to an activated state by inhibiting IL-2 secretion and cellular proliferation. (thermofisher.com)
  • CTLA4 (Cytotoxic T-Lymphocyte Antigen 4) is a CD28-family receptor expressed on mainly CD4+ T cells. (thermofisher.com)
  • Cytotoxic T lymphocyte -associated antigen -4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. (bvsalud.org)
  • Because it greatly resembled CD28 and was activated by the same binding molecules, the initial thought was that CTLA-4 was another co-stimulator. (mdanderson.org)
  • CTLA-4 is cross-wired with the antigen receptor and CD28, so the brake is activated at the same time to help ensure that the immune response doesn't go on and on, destroying healthy cells," Allison says. (mdanderson.org)
  • The protein encoded by this gene is a membrane receptor that is activated by the binding of CD28 or CTLA-4. (genecards.org)
  • T-cell proliferation and cytokine production is induced by the binding of CD28, binding to CTLA-4 has opposite effects and inhibits T-cell activation. (genecards.org)
  • It has homology with the T cell antigen CD28, and like CD28, is a ligand for CD80 and CD86. (beckman.com)
  • Professional antigen-presenting cells activate naive T cells through MHC-II complex/TCR and B7(CD80/86)/CD28 co-stimulatory binding. (biomedcentral.com)
  • A seminal study [ 4 ] revealed that CTLA-4 inhibits T cell activation by competing with CD28 for B7 ligands early in the adaptive immune response. (biomedcentral.com)
  • Publications] Azuma M.: 'B70 antigen is a second ligand for CTLA-4 and CD28. (nii.ac.jp)
  • Although both CTLA-4 and CD28 can bind to the same ligands, CTLA-4 binds to B7-1 and B7-2 with a 20-100 fold higher affinity than CD28 and is involved in the down-regulation of the immune response (2-6). (rndsystems.com)
  • Alternative splicing generates a 30-kDa soluble isoform that lacks the transmembrane segment and retains the ability to bind CD28 and CTLA-4 and an isoform that lacks the second Ig-like domain and the transmembrane segment (8). (rndsystems.com)
  • Both human and mouse B7-1 and B7-2 can bind to either human or mouse CD28 and CTLA-4 (1). (rndsystems.com)
  • More recently, it has been suggested that CTLA4 may function in vivo by removing B7-1 and B7-2 from the membranes of antigen cells, stopping them from triggering CD28. (prospecbio.com)
  • CD28 and CTLA-4 share similar ligands called CD80 (B7.1) and CD86 (B7.2). (thefreedictionary.com)
  • Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population. (semanticscholar.org)
  • CD86 and CD80 bind as ligands to costimulatory molecule CD28 on the surface of all naïve T cells, and to the inhibitory receptor CTLA-4 (cytotoxic T-lymphocyte antigen-4, also known as CD152). (wikipedia.org)
  • CD28 and CTLA-4 have important, but opposite roles in the stimulation of T cells. (wikipedia.org)
  • Binding to CD28 promotes T cell responses, while binding to CTLA-4 inhibits them. (wikipedia.org)
  • The interaction between CD86 (CD80) expressed on the surface of an antigen-presenting cell with CD28 on the surface of a mature, naive T-cell, is required for T-cell activation. (wikipedia.org)
  • Both CD80 and CD86 bind CTLA-4 with higher affinity than CD28. (wikipedia.org)
  • This allows CTLA-4 to outcompete CD28 for CD80/CD86 binding. (wikipedia.org)
  • Between CD80 and CD86, CD80 appears to have a higher affinity for both CTLA-4 and CD28 than CD86. (wikipedia.org)
  • Since CTLA-4 binds to CD86 with higher affinity than CD28, the co-stimulation necessary for proper T-cell activation is also affected. (wikipedia.org)
  • Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a member of the CD28 superfamily and is a negative regulator of T cell-mediated immune responses. (biocare.net)
  • CTLA-4 primarily inactivates T-cell activity by competing with the CD28 costimulatory molecule (3). (biocare.net)
  • and thus CTLA-4 competes with CD28 function in T-cell survival, proliferation, and recruitment (3,4). (biocare.net)
  • Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. (biocare.net)
  • B70 antigen is a second ligand for CTLA-4 and CD28. (biocare.net)
  • This protein is homologous to the CD28/CTLA-4 proteins. (biolegend.com)
  • Mice depleted of CD8 + T cells from birth by antibody treatment develop a lymphoproliferative disorder similar in onset and severity to unmanipulated CTLA-4 −/− mice, whereas lymphoproliferation does not occur in CTLA-4 −/− mice depleted of CD4 + T cells from birth. (pnas.org)
  • To explore this, we analyzed immune-related adverse events and immune responses in metastatic melanoma patients treated with ipilimumab, a fully human anti-CTLA-4 monoclonal antibody. (pnas.org)
  • Because CTLA-4 is constitutively expressed on T regs , antibodies that bind CTLA-4 have also been recently reported to operate independently of CTLA-4-B7 interactions by triggering antibody-dependent cell-mediated cytotoxicity (ADCC) and Fc receptor-mediated elimination of T regs within tumors in mouse models ( 6 - 8 ). (sciencemag.org)
  • The ELISA (enzyme-linked immunosorbent assay) is a well-established antibody-based tool for detecting and quantifying antigens of interest. (biocompare.com)
  • The following antibody was used in this experiment: CD152 (CTLA-4) Monoclonal Antibody (UC10-4B9), PE, eBioscience™ from Thermo Fisher Scientific, catalog # 12-1522-82, RRID AB_465879. (thermofisher.com)
  • Description: The UC10-4B9 monoclonal antibody reacts with mouse CD152, also known as the cytotoxic T lymphocyte antigen-4 (CTLA-4). (thermofisher.com)
  • Mouse CTLA-4 antibodies with has blocking effect against CD80/CD86 binding with CTLA4 can serve as a great surrogate antibody in mouse model. (genscript.com)
  • The appropriate concentrations may be affected by secondary antibody affinity, antigen concentration, the sensitivity of the method of detection, temperature, the length of the incubations, and other factors. (genscript.com)
  • The following antibody was used in this experiment: CTLA-4 Monoclonal Antibody (WKH 203), PE from Thermo Fisher Scientific, catalog # MA5-17587, RRID AB_2538977. (thermofisher.com)
  • Security from colitis is certainly abrogated by shot of preventing antibody (Ab) against CTLA-4 recommending that CTLA-4 is essential for immune legislation within this model program (28, 29). (tas-102.net)
  • Rat anti-human monoclonal antibody against HLA DR (1:200 dilution, clone YE2/36HLK, Abcam Biotechnology, Cambridge, MA) and mouse anti-human monoclonal antibody against HLA class I (1:200 dilution, clone A4, eBioscience, San Diego, CA) were then applied at 4 C overnight. (exatecan-mesylate.com)
  • We used a neutralizing antibody to block CTLA-4 interaction with its ligands CD80 and CD86 during infection of mice with the nematode, Nippostrongylus brasiliensis. (nih.gov)
  • We found that anti-CTLA-4 mAb treatment induced a profound 20-fold increase in IL-5 production (Fig. 1 a) and a massive 40-fold increase in IL-4 production (Fig. 2 a) from the draining mediastinal lymph node at day 6 after infection compared to mice given control antibody. (nih.gov)
  • The combination of Id2kd-N2a cell vaccination with anti CTLA-4 plus anti PD-L1 antibody treatment proved to be highly effective, even against established neuroblastoma tumors, resulting in cure of treated mice ( n = 16) as well as long-term immune memory (6 months). (prolekare.cz)
  • A mouse experiment in 1995 using an antibody against CTLA-4 worked so well that Allison wanted to repeat it immediately. (mdanderson.org)
  • He didn't know which mice, all with colon cancer, had been treated with the antibody to block CTLA-4. (mdanderson.org)
  • Immune-related adverse events are common and well-documented in patients treated with ipilimumab, a cytotoxic T-lymphocyte antigen-4 monoclonal antibody approved for the treatment of metastatic and stage III melanoma. (bireme.br)
  • The T cells are genetically modified through transduction with a retroviral vector expressing scFv of anti-PSMA antibody linked to CTLA and 4 and CD3ζ signaling domains. (creative-biolabs.com)
  • Depletion of these gMDSCs with a systemic anti-Ly6G antibody (1A8) did not change CD8/4 + T-cell or NK cell accumulation but restored tumor T-cell and NK cell activation and draining lymph node antigen-specific T-lymphocyte activation that was lost with tumor progression. (aacrjournals.org)
  • There are currently no images for CD1.1 antigen Antibody (NBP1-28362). (novusbio.com)
  • Our group conducted the first preoperative clinical trial with the anti-CTLA-4 antibody ipilimumab in 12 patients with localized urothelial carcinoma of the bladder. (aacrjournals.org)
  • Six patients were treated with 3 mg/kg/dose of anti-CTLA-4 and six patients were treated with 10 mg/kg/dose of antibody. (aacrjournals.org)
  • Most clinical trials of CTLA-4 blockade have been conducted in the metastatic disease setting, which allows for correlation of treatment with clinic outcomes but not for detailed immunologic studies on tumor-infiltrating lymphocytes to evaluate how the antibody impacts human immune responses. (aacrjournals.org)
  • In our presurgical study, we found that anti-CTLA-4 had a tolerable safety profile without an increase in perioperative complications after a short course of antibody. (aacrjournals.org)
  • 1. Use of an anti-CTLA-4 antibody or a fragment thereof in the manufacture of a medicament for treating melanoma. (epo.org)
  • The claims related to the use of a blocking anti-CTLA-4 antibody or a blocking fragment thereof in the manufacture of a medicament for treating melanoma. (epo.org)
  • Firstly, the only evidence of successful treatment of tumours by treatment with an antibody blocking the binding of CLTA-4 with its ligand was for carcinoma and fibrosarcoma in document D3. (epo.org)
  • GigaGen's study concludes that different immunization protocols generated a diverse response to each antigen, and thus performing multiple immunization strategies in parallel can yield greater overall antibody diversity. (prnewswire.com)
  • Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. (harvard.edu)
  • Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. (harvard.edu)
  • FDA approved Ipilimumab (IgG1 isotype), a monoclonal antibody to CTLA-4, was the first immunotherapeutic drug directed toward CTLA-4 inhibition to demonstrate overall survival benefit in metastatic melanoma (1,7). (biocare.net)
  • The first class of immune checkpoints approved by US Food and Drug Administration (FDA) for metastatic melanoma patients included an antibody anti-Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) (ipilimumab), a co-inhibitory receptor expressed on the surface of T-cells. (biomedcentral.com)
  • The GG genotype was associated with a significantly higher mean serum aspartate transaminase level (P =. 03), greater frequency of antibodies to thyroid microsomal antigens (P =.004) and was found more commonly in patients with HLA DRB1*0301 (P =.02). (nih.gov)
  • Anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibodies, such as ipilimumab, have generated measurable immune responses to Melan-A, NY-ESO-1, and gp100 antigens in metastatic melanoma. (nih.gov)
  • Targeting CTLA-4 as an anticancer strategy: Following proof-of-concept studies in animals, fully human anti-CTLA-4 antibodies were developed and 2 are undergoing clinical evaluation. (nih.gov)
  • Two monoclonal antibodies to human CTLA-4 have been found to elicit objective and durable tumor responses in clinical trials ( , 10 - , 14 ). (pnas.org)
  • The mechanism by which anti-CTLA-4 antibodies induces antitumor responses is controversial. (sciencemag.org)
  • Monoclonal antibodies (mAbs) that block CTLA-4 interactions with B7 may enhance effector T cell (T eff ) function ( 2 ) and may also inhibit regulatory T cell (T reg ) activity ( 3 , 4 ), leading to regression of established tumors in mouse models ( 5 ). (sciencemag.org)
  • This central regulatory role led to the development of antibodies designed to block CTLA-4 activity in vivo, aiming to enhance immune responses against cancer. (rupress.org)
  • We conclude that the combination of direct enhancement of T eff cell function and concomitant inhibition of T reg cell activity through blockade of CTLA-4 on both cell types is essential for mediating the full therapeutic effects of anti-CTLA-4 antibodies during cancer immunotherapy. (rupress.org)
  • Based on the recognition of the importance of CTLA-4 in the regulation of immune responses, blocking antibodies against both mouse and human forms have been investigated for their potential to boost immunological responses against cancer. (rupress.org)
  • Despite growing experience of their use in the treatment of human cancers, the precise mechanisms underpinning CTLA-4-mediated control of the immune response and, more specifically, the antitumor activity of anti-CTLA-4 antibodies, remain elusive. (rupress.org)
  • The present invention relates to antibodies that bind to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). (google.com)
  • Clinical trials using antibodies that block the ligation of PD-1 (nivolumab, pembrolizumab) or CTLA-4 (ipilimumab), with their ligands, revealed them to be efficient in more than 15 cancer types, including metastatic melanoma, bladder carcinoma, non-small cell lung cancer, and breast and renal cell carcinoma [ 9 - 12 ]. (hindawi.com)
  • In the US, Ipilimumab (ipilimumab systemic) is a member of the drug class anti-CTLA-4 monoclonal antibodies and is used to treat Melanoma and Melanoma - Metastatic . (drugs.com)
  • Collectively, the immunotherapy principle consists in the modulation of the immune cells activity, predominantly T cells, using adoptive cell transfer, chimeric-antigen receptor T-cells, or monoclonal antibodies (mAbs) ( 5 , 6 ). (frontiersin.org)
  • Although the role of antibodies that target CTLA-4 and PD-1 has been established in solid tumor malignancies and Food and Drug Administration approved for melanoma and non-small cell lung cancer, there remains a desperate need to incorporate immune checkpoint inhibition in hematologic malignancies. (aspetjournals.org)
  • Ipilimumab and tremelimumab are antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4). (uptodate.com)
  • We validated this signature in a second set of 39 patients with melanoma who were treated with anti-CTLA-4 antibodies. (uptodate.com)
  • The invention provides antibodies that specifically bind to the LG4-5 modules of the G domain of laminin .alpha.4. (patents.com)
  • Antibodies that specifically bind to toxins of C. difficile, antigen binding portions thereof, and methods of making and using the antibodies and antigen. (patents.com)
  • get custom DNA sequences encoding chimeric antibodies that you design delivered in as few as 4 days . (genscript.com)
  • Chimeric Anti-CD14 IGG2/4 Hybrid Antibodies for Therapeutic Intervention in Pig and Human Models of Inflammation. (genscript.com)
  • Application of protein microarrays for multiplexed detection of antibodies to tumor antigens in breast cancer. (harvard.edu)
  • NCR inhibitors are monoclonal antibodies against CTLA-4 (ipilimumab) or PD-1/PD-L1 (i.e. nivolumab) can activate the immune system , enhancing T-cell proliferation and activity against tumors. (medindia.net)
  • CTLA-4 blockade increases antigen-specific CD8(+) T cells in prevaccinated patients with melanoma: three cases. (nih.gov)
  • Blockade of inhibitory signals mediated by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been shown to enhance T cell responses and induce durable clinical responses in patients with metastatic melanoma. (pnas.org)
  • CTLA-4 blockade in patients with metastatic castration-resistant prostate cancer and metastatic melanoma resulted in both expansion and loss of T cell clonotypes, consistent with a global turnover of the T cell repertoire. (sciencemag.org)
  • Two fully human mAbs to CTLA-4, ipilimumab and tremelimumab, have undergone phase 3 studies in human studies ( 9 , 10 ), with the former being U.S. Food and Drug Administration-approved in the treatment of metastatic melanoma. (sciencemag.org)
  • Your search returned 2 B melanoma antigen family member 3 ELISA ELISA Kit across 1 supplier. (biocompare.com)
  • We developed a mouse expressing human instead of mouse CTLA-4, allowing us to evaluate the independent contributions of CTLA-4 blockade of each T cell compartment during cancer immunotherapy in an in vivo model of mouse melanoma. (rupress.org)
  • Outside the skin, melanocytes occur in eye, mucosal epithelia and meninges [ 4 ] and therefore melanomas can be divided according to the place of origin to the most common cutaneous melanoma, uveal melanoma and mucosal melanoma [ 5 ]. (mdpi.com)
  • The checkpoint regulators CTLA-4 and PD-1 expressed in immune cells were successfully targeted for immunotherapies: in metastatic melanoma patients the anti-CTLA-4 ipilimumab significantly extended the median OS to 10.1 m, in phase III, compared to 6.4 m for the control group, enabling an unprecedented durable tumor regression of 46,6% at 1 y. and 23,5% at 2 y. [ 8 ]. (hindawi.com)
  • Fig. 6: MARIA scores predict melanoma HLA-II-presented antigens and are associated with post-vaccine CD4 + T cell responses. (nature.com)
  • High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4 + T cells in human melanoma. (nature.com)
  • To determine if CD4 + ICOS hi T cells could be a correlative marker for clinical outcome after treatment with anti-CTLA-4, a cohort of metastatic melanoma patients was studied retrospectively for frequency of CD4 + ICOS hi T cells and survival. (aacrjournals.org)
  • Moreover, the concept of CTLA-4 blockade, termed checkpoint blockade, has been used in the clinical setting and has shown promise in the induction of antitumor responses in patients with melanoma, prostate cancer, and lymphoma ( 8 - 15 ). (aacrjournals.org)
  • Document D5, an editorial from the same issue of the journal 'Science', provided a commentary on document D3 and was the only document in the state of the art that mentioned melanoma in connection with a CTLA-4 blockade. (epo.org)
  • However, neither document D3 or D5 gave the skilled person a reasonable expectation of successfully treating melanoma by CTLA-4 blockade for several reasons. (epo.org)
  • Genetic basis for clinical response to CTLA-4 blockade in melanoma. (uptodate.com)
  • Anti-CTLA-4 treatment prolongs overall survival in patients with melanoma. (uptodate.com)
  • RESULTS: Malignant melanoma exomes from 64 patients treated with CTLA-4 blockade were characterized with the use of massively parallel sequencing. (uptodate.com)
  • CONCLUSIONS: These findings define a genetic basis for benefit from CTLA-4 blockade in melanoma and provide a rationale for examining exomes of patients for whom anti-CTLA-4 agents are being considered. (uptodate.com)
  • Well-defined melanoma antigens as progression markers for melanoma: insights into differential expression and host response based on stage. (harvard.edu)
  • Immunization using autologous dendritic cells pulsed with the melanoma-associated antigen gp100-derived G280-9V peptide elicits CD8+ immunity. (harvard.edu)
  • CTLA-4 blockade with ipilimumab induces significant clinical benefit in a female with melanoma metastases to the CNS. (harvard.edu)
  • Another CTLA-4 inhibitor, tremelimumab (IgG2 isotype), has also proven successful in metastatic melanoma and other malignancies (1,7). (biocare.net)
  • Cytotoxic T-lymphocyte antigen-4 blockade in melanoma. (biocare.net)
  • Opdivo is an investigational PD-1 immune checkpoint inhibitor currently approved in Japan for the treatment of patients with unresectable melanoma, and Yervoy is a CTLA-4 immune checkpoint inhibitor approved in the U.S. and more than 40 countries for patients with unresectable or metastatic melanoma. (eurekalert.org)
  • Tumor escape may be related to antigen loss or lack of MHC expression necessary for immune activity. (nih.gov)
  • In light of the multiple potential checkpoint targets, the article by Duraiswamy and colleagues ( 2 ) from our laboratory set out to dissect the potential of cotargeting two key components of T-cell dysregulation in tumors, cytotoxic T lymphocyte-associated protein 4 (CTLA-4), and programmed cell death 1 (PD-1) to potentially synergize their efficacies in tumor eradication. (aacrjournals.org)
  • Furthermore, we aimed at enhancing checkpoint blockades with a whole tumor antigen vaccination strategy. (aacrjournals.org)
  • CTLA-4 and PD-1 were coexpressed in a subset of tumor-infiltrating lymphocytes (TIL), which showed the greatest level of inhibition of T-cell function, including antigen recognition and cytokine release. (aacrjournals.org)
  • In both tumor models, one can identify and track tumor-specific CD8 + T cells directed against known antigens of CT26 or ID8-VEGF tumors, namely the gp70 423-431 peptide of AH-1 and the FR 161-169 of the folate receptor, respectively. (aacrjournals.org)
  • Reproducible results were found in both tumor models, whereby the frequency of IFNγ + , TNFα + , IL2 + , or CD107a/b + responder cells was approximately double among the single PD-1 + (PD-1 + CTLA-4 − ) TILs relative to the double-positive (PD-1 + CTLA-4 + ) TILs. (aacrjournals.org)
  • Thus, our work clearly demonstrated that double PD-1/CTLA-4 blockade can rescue double-positive PD-1 + CTLA-4 + TILs from their severely dysfunctional status and partly restore their response to tumor antigen. (aacrjournals.org)
  • Blockade of CTLA-4 signaling has been shown to augment T cell responses and induce tumor rejection in a number of animal models ( , 7 - , 9 ). (pnas.org)
  • However, the functional impact of anti-CTLA-4 therapy on human immune responses to antigens present on tumor cells is not yet fully understood. (pnas.org)
  • In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti- tumor effects in a prostate cancer mouse model. (bvsalud.org)
  • Acting in concert with a costimulatory CTLA-4 checkpoint inhibitor, Id2kd-N2a whole tumor cell vaccination generated a potent tumor-specific T-cell response, capable of eradicating established tumors in 60% of mice [ 13 , 14 ]. (prolekare.cz)
  • When CTLA-4 was used alone without vaccination in the wild-type (WT) N2a model or the AgN2a model, only 40% and 0% of mice were cured of tumor, respectively [ 14 ]. (prolekare.cz)
  • CTLA-4 blockade plus Id2kd vaccination induces tumor specific T-cell expansion and tumor infiltration in mice, in which the infiltrating CD8 T cells are characterized by PD1 expression. (prolekare.cz)
  • Intriguingly, the upregulation of tumor programmed death-L1 and cytotoxic T lymphocyte-associated antigen 4 alters the metabolic programme of T cells and drives their exhaustion. (frontiersin.org)
  • Since the cells and the molecules of the immune system are a fundamental component of the tumor microenvironment (TME), cancer immunotherapy has emerged as a powerful new therapeutic approach to boost antitumor immunity response ( 4 ). (frontiersin.org)
  • T cells require binding of their T cell receptor (TCR) to the peptide/human leukocyte antigen complex (pHLA) that is expressed on the target, as well as binding of the T cell costimulatory receptors to their cognate ligands that are expressed by the tumor or antigen presenting cell (APC). (aspetjournals.org)
  • Using these MOC models, we have demonstrated an inverse relationship between accumulation of granulocytic MDSCs (gMDSCs) and effector immune cells (CD8/4 + T-cells, and NK cells) in the tumor microenvironment. (aacrjournals.org)
  • CTLA-4 blockade alone induced tumor regression in a subset of mice and a marked delay in others. (aacrjournals.org)
  • However, gMDSC depletion plus CTLA-4 blockade resulted in complete tumor rejection and development of immunologic memory in all treated mice. (aacrjournals.org)
  • Manipulation of CTLA-4 has recently gained enormous attention in the field of tumor immunotherapy ( 1 ). (sciencemag.org)
  • Blockade of CTLA-4 has led to enhanced T-cell activation in animal models ( 5 , 6 ), and mechanistic studies have shown that animals treated with anti-CTLA-4 have an increased ratio of effector to regulatory T cells, which correlates with tumor regression ( 7 ). (aacrjournals.org)
  • To circumvent these issues, we designed a clinical trial using anti-CTLA-4 in the preoperative setting so that we might obtain tumor tissues for immunologic studies and attempt to identify biomarkers in peripheral blood that might correlate with those in tumor tissues. (aacrjournals.org)
  • Tumor cells express PD-L1, which inhibits immune activity by binding to T cell PD-1 receptors, despite TCR recognition of target tumor antigens presented on tumor cell MHC-1 complex. (biomedcentral.com)
  • It has long been debated whether cancer cells were bearing "tumor-specific" antigens, absent from normal cells, which could in principle cause the elimination of the tumor by the immune system. (wikipedia.org)
  • It is now proven that tumor-specific antigens exist and that patients mount spontaneous T cell responses against such antigens. (wikipedia.org)
  • Hence, a new antigen is present only on the tumor cells. (wikipedia.org)
  • Genetic processes other than point mutations can lead to tumor-specific antigens. (wikipedia.org)
  • In cancer patients, about one half of the highly tumor-specific antigens recognized by spontaneous T cell responses are encoded by mutated genes, the other half being encoded by cancer-germline genes. (wikipedia.org)
  • In some patients, the majority of the tumor-specific T cells recognize mutated antigens. (wikipedia.org)
  • The contribution of these antigens to tumor immunogenicity is expected to vary according to the mutation rate: higher in lung carcinomas arising in tobacco smokers, in melanomas owing to mutations induced by UV and in the 15% of colorectal carcinomas that have hypermutated DNA owing to defects in the DNA mismatch repair pathway. (wikipedia.org)
  • Cancer-germline genes are an important source of tumor-specific antigens. (wikipedia.org)
  • CTLA-4 blockade activates T cells and enables them to destroy tumor cells. (uptodate.com)
  • and (4) reduction in total tumor burden during or after the appearance of new lesion(s) after week 12. (uptodate.com)
  • After ipilimumab induction, patients experienced a robust, although sometimes transient, antigen-specific response for gp100 (IMF-32 and IMF-24) or NY-ESO-1 (IMF-11) and produced polyfunctional intracellular cytokines. (nih.gov)
  • We hypothesized that CTLA-4 blockade by ipilimumab may promote T cells responses to this prototypical antigen. (pnas.org)
  • After ipilimumab induction, patients experienced a strong, although sometimes transient, antigen-specific response for gp100 (IMF-32 and IMF-24) or NY-ESO-1 (IMF-11) and produced polyfunctional intracellular cytokines. (exatecan-mesylate.com)
  • Arm 1 (Immediate Treatment): Ipilimumab Q3wks x 4 started 1 day following the final dose of SipT (Day 0). (clinicaltrials.gov)
  • The median number of ipilimumab doses received was 4. (thejns.org)
  • Hypophysitis after treatment with a CTLA-4 inhibitor, such as ipilimumab, can approach 12%, though it is much less common with the checkpoint inhibitors that target PD-1 and PD-L1. (thefreedictionary.com)
  • T Lymphocyte Activation Antigen CD80 (Activation B7-1 Antigen or CTLA 4 Counter Receptor B7.1 or CD80) - Cluster of differentiation 80 or CD80 or B7-1 is a protein found on dendritic cells, activated B cells and monocytes. (reportbuyer.com)
  • CTLA4 or CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that, functioning as an immune checkpoint, downregulates immune responses. (creative-biolabs.com)
  • Sensitized CD8 + T-cells are targeted to melanocyte differentiation antigens and destroy melanocytes either as the primary event in vitiligo or as a secondary promotive consequence. (clinsci.org)
  • Cluster of Differentiation 86 (also known as CD86 and B7-2) is a protein constitutively expressed on dendritic cells, Langerhans cells, macrophages, B-cells (including memory B-cells), and on other antigen-presenting cells. (wikipedia.org)
  • Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), also known as CD152, is one of the first well studied immune checkpoint molecules. (genscript.com)
  • CD80 dimers on the antigen presenting cells (APCs) bridge CTLA4/CD152 dimers on T-cells in a periodic zipper-like arrangement. (genecards.org)
  • The CD152 antigen, also called CTLA4, is an integral membrane protein belonging to the immunoglobulin superfamily, which is expressed either as a 30 kDa monomer or as a disulfide-linked homodimer. (beckman.com)
  • Coating antigen: CTLA4-Fc, 1 µg/ml. (genscript.com)
  • Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines . (bvsalud.org)
  • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) is a Protein Coding gene. (genecards.org)
  • To examine the effect of restricting the CD4 + TCR repertoire on the phenotype of CTLA-4-deficient mice and to assess the influence of CTLA-4 on peptide-specific CD4 + T cell responses in vitro , an MHC class II-restricted T cell receptor (AND TCR) transgene was introduced into the CTLA-4 −/− animals. (pnas.org)
  • We demonstrate that CTLA-4- or PD-1-based iCARs can selectively limit cytokine secretion, cytotoxicity, and proliferation induced through the endogenous T cell receptor or an activating chimeric receptor. (sciencemag.org)
  • The initial effect of the iCAR is temporary, thus enabling T cells to function upon a subsequent encounter with the antigen recognized by their activating receptor. (sciencemag.org)
  • T Lymphocyte Activation Antigen CD80 (Activation B7-1 Antigen or CTLA 4 Counter Receptor B7.1 or CD80) pipeline Target constitutes close to 10 molecules. (reportbuyer.com)
  • The latest report T Lymphocyte Activation Antigen CD80 - Pipeline Review, H2 2018, outlays comprehensive information on the T Lymphocyte Activation Antigen CD80 (Activation B7-1 Antigen or CTLA 4 Counter Receptor B7.1 or CD80) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (reportbuyer.com)
  • It also reviews key players involved in T Lymphocyte Activation Antigen CD80 (Activation B7-1 Antigen or CTLA 4 Counter Receptor B7.1 or CD80) targeted therapeutics development with respective active and dormant or discontinued projects. (reportbuyer.com)
  • To determine the effects of CTLA-4 blockade on the T cell repertoire, we used next-generation deep sequencing to measure the frequency of individual rearranged T cell receptor β (TCRβ) genes, thereby characterizing the diversity of rearrangements, known as T cell clonotypes. (sciencemag.org)
  • Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a co-inhibitory receptor that controls T cell activation during initiation and maintenance of adaptive immune responses. (sciencemag.org)
  • However, in the context of cancer therapy, blocking the immune-checkpoints CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) and/or PD-1/PD-L1 (programmed death 1 receptor and PD-1 receptor ligand 1) significantly facilitates immune cell activation, thereby generating durable clinical responses in cancer patients [ 3 , 4 ]. (hindawi.com)
  • In addition, the ligation of B7-1 and B7-2, which are specifically expressed on antigen-presenting cells (APCs), to their receptor CTLA-4 prevents T cell activation. (hindawi.com)
  • The recent observation that neutralization or genetic deletion of the T lymphocyte receptor CTLA-4 allows enhanced T cell reactivity offers new opportunities for immunotherapy against infectious agents. (nih.gov)
  • Programmed cell death 1 (PD1) is another immune checkpoint receptor and is more broadly expressed on T cells than CTLA-4 [ 8 , 9 ]. (prolekare.cz)
  • The vector of anti-PSMA chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human PSMA. (creative-biolabs.com)
  • Thirdly, at the effective date of the patent, it was not generally established that blocking the binding of CTLA-4 to its receptor would always lead to an immune boost. (epo.org)
  • LAG3, a co-receptor of the T cell receptor, is structurally highly homologous to CD4 and shares its main ligand MHC class II, binding to it with a much higher affinity than CD4 [ 4 ]. (springer.com)
  • T cell activation is initiated when a T cell receptor (TCR) binds to an antigen presented on the major histocompatibility complex (MHC) of professional antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs). (biomedcentral.com)
  • This occurs because each T cell is endowed with a highly specific receptor that can bind to an antigen present at the surface of another cell. (wikipedia.org)
  • There a process named central tolerance eliminates the T cells that have a receptor recognizing an antigen present on normal cells of the organism. (wikipedia.org)
  • CTLA-4-mediated costimulation inhibits T cell-proliferative and cytokine responses in vitro , and blockade of CTLA-4/ligand interaction enhances T cell responses in vivo ( 4 ). (pnas.org)
  • The nature of TCR-ligand interaction that initiates the lymphoproliferation and the extent to which individual naive CD4 + T cells become dysregulated by the absence of CTLA-4 in vivo is unknown. (pnas.org)
  • In addition to in vitro binding measurements, MARIA is trained on peptide HLA ligand sequences identified by mass spectrometry, expression levels of antigen genes and protease cleavage signatures. (nature.com)
  • Fig. 4: MARIA trained on human HLA-DQ ligand peptides identified celiac-related gluten antigens. (nature.com)
  • The targets of such therapies are CTLA-4 and PD-1 receptors, both expressed on the T cell surface, and PD-1 ligand PD-L1. (biomedcentral.com)
  • To become activated, lymphocyte must engage both antigen and costimulatory ligand on the same antigen-presenting cell. (wikipedia.org)
  • Identification of an alternative CTLA-4 ligand costimulatory for T cell activation. (biocare.net)
  • this occurs in response to competitive binding of CD80/CD86 on the APC by CTLA-4 on the T cell. (nih.gov)
  • Coating antigen: CD86, 0.5 µg/ml. (genscript.com)
  • It acts as an "off" switch when bound to CD80 or CD86 on the surface of antigen-presenting cells. (creative-biolabs.com)
  • 2. Administration of anti-LFA-1/ICAM-1, anti-VLA-4/VCAM-1, anti-CD2/CD48, or anti-CD80/CD86 mAbs could induce cardiac, bowel, or plancreatic islet allograft tolerance. (nii.ac.jp)
  • 4. Lethal GVHD after bone marrow transplantation was prevented by the administration of anti-CD80/CD86 mAbs. (nii.ac.jp)
  • costimulatory ligands CD80 and CD86 can be found on professional antigen presenting cells such as monocytes, dendritic cells, and even activated B-cells. (wikipedia.org)
  • Interaction between CTLA-4 and CD80/CD86 leads to delivery of negative signals into T cells and reduction of number of costimulatory molecules on the cell surface. (wikipedia.org)
  • Treg expression of CTLA-4 can effectively downregulate both CD80 and CD86 on APCs, suppress the immune response and lead to increased anergy. (wikipedia.org)
  • The double-positive population also expressed higher levels of additional inhibitory receptors, such as 2B4, LAG-3, and TIM-3, and exhibited higher levels of CD44 and lower levels of CD62L and CD127, suggesting that the double-positive TILs represent an antigen-experienced, functionally exhausted effector cell phenotype. (aacrjournals.org)
  • On the basis of the physiological paradigm of immune inhibitory receptors, we designed antigen-specific inhibitory chimeric antigen receptors (iCARs) to preemptively constrain T cell responses. (sciencemag.org)
  • Whereas each T cell recognizes a single antigen, collectively the T cells are endowed with a large diversity of receptors targeted at a wide variety of antigens. (wikipedia.org)
  • The protective effector function of T cells may be compromised by inhibitory receptors such as CTLA-4 and PD-L1 (3, 5). (thefreedictionary.com)
  • population that are differentially expressed by discrete Treg subsets, according to activation and memory status (CD45RA naive and CD45RO memory), chemotactic profile (chemokine receptors like CCR4 and CCR9), suppressive functions ( CTLA-4 , CD39, and CD73), and more [20]. (thefreedictionary.com)
  • Chimeric antigen receptors containing mesothelin antigen binding domains are disclosed. (patents.com)
  • When given a lethal secondary infection, CD8 and CD4 T cells upregulate several coinhibitory receptors, including PD-1, TIM-3, 4-1bb, and CTLA-4. (asm.org)
  • T cell exhaustion is a state of cellular hyporesponsiveness that occurs in response to continued antigen stimulation or inflammation, wherein T cells produce fewer cytokines and cytotoxic molecules, lower expression levels of activating receptors, and increased expression levels of inhibitory receptors ( 1 ). (asm.org)
  • French scientists identified another T cell surface protein they named Cytotoxic T-Lymphocyte Antigen 4, or CTLA-4. (mdanderson.org)
  • The "Checkpoint blockade" that utilizes mAbs specific to cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein 1 pathway (PD-1/PD-L1), is arising as a newer strategy used to fight cancer and one of the most promising immunotherapies ( 7 , 8 ). (frontiersin.org)
  • Cytotoxic-T-lymphocyte antigen (CTLA-4) and programmed cell death protein 1 (PD-1) are the two most commonly targeted immune checkpoint molecules. (aspetjournals.org)
  • 3 ) provide evidence that an intracellular protein, lipopolysaccharide-responsive and beige-like anchor protein (LRBA) controls CTLA-4 expression and thereby influences immune self-tolerance. (sciencemag.org)
  • Discovery of the immune checkpoints cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) as key regulators of the adaptive immune response motivated the development of immune checkpoint blockade (ICB) therapeutics targeting these pathways. (biomedcentral.com)
  • In recent years, cytotoxic T lymphocyte protein-4 ( CTLA-4 ) and programmed cell death protein-1 (PD-1) have shown promise as novel therapeutic targets in some cancers [7-10]. (thefreedictionary.com)
  • GigaGen's deep understanding of immune dysregulation is enabled by industry-leading technology that quickly captures the genetic makeup of entire immune repertoires to analyze B cells at a rate of millions per hour, while simultaneously identifying their antigen and protein binders. (prnewswire.com)
  • Vaccination induced a measurable antigen-specific T-cell response that increased following CTLA-4 blockade, potentially "boosting" the vaccine-primed response. (nih.gov)
  • Increased cytokine production in response to CTLA-4 blockade was due to increased lymphocyte numbers per mediastinal lymph node as well as increased cytokine production. (nih.gov)
  • We elucidated a neoantigen landscape that is specifically present in tumors with a strong response to CTLA-4 blockade. (uptodate.com)
  • Interruption of immune inhibitory pathways via CTLA-4 blockade appears to be a promising strategy for cancer immunotherapy. (nih.gov)
  • We also describe preclinical and clinical results that indicate manipulation of CTLA-4 has considerable promise as a strategy for the immunotherapy of cancer. (nih.gov)
  • The most appealing element to this approach, termed antigen-specific immunotherapy (ASI), has been that it not only provides an effective means of controlling the autoimmune response via induction or restoration of β-cell-specific tolerance, but that it may achieve these goals without major concerns over safety and certainly without the specter of immune suppression. (diabetesjournals.org)
  • Beneficial effects of antigen-specific immunotherapy (ASI) on the pathological immune responses that result in type 1 diabetes. (diabetesjournals.org)
  • Schellhammer PF, Chodak G, Whitmore JB, Sims R, Frohlich MW, Kantoff PW (2013) Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the immunotherapy for prostate adenocarcinoma treatment (IMPACT) trial. (springermedizin.de)
  • Importantly, PD-1 + CTLA-4 − and PD-1 + CTLA-4 + TILs were sorted from untreated tumors and tested for response ex vivo to the above cognate peptide in each model, which was presented in these experiments by pulsed splenocytes. (aacrjournals.org)
  • The recognition of mutation-induced antigens on tumors by T cells is only one aspect of a more general phenomenon which can rightly be named: T cell immunosurveillance of the integrity of the genome. (wikipedia.org)
  • Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis. (nih.gov)
  • The gene encoding cytotoxic T-lymphocyte antigen-4 (CTLA-4) on chromosome 2q33 may also influence autoimmunity. (nih.gov)
  • Interestingly, young AND TCR + CTLA-4 −/− mice carrying a null mutation in the rag-1 gene remain healthy and the T cells maintain a naive phenotype until later in life. (pnas.org)
  • CTLA-4 was originally identified as a gene that was specifically expressed by cytotoxic T lymphocytes. (novusbio.com)
  • Heterozygosity in CTLA-4 gene and severe preeclampsia. (biomedsearch.com)
  • A49G polymorphism in position 49 of exon-1 of the CTLA-4 gene was studied by the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method. (biomedsearch.com)
  • Whether the observed association results from linkage imbalance with other loci on chromosome 2 or other polymorphisms of the CTLA-4 gene or even from a preferential transfer and/or expression of one allele from a heterozygous mother to the fetus will be the subject of future investigations. (biomedsearch.com)
  • Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism confers susceptibility to thyroid associated orbitopathy. (ox.ac.uk)
  • We show that the presence and severity of TAO are associated with an allele of the cytotoxic T lymphocyte antigen-4-gene. (ox.ac.uk)
  • Consequently, we constructed a DNA vaccine containing the PSCA and the CTLA-4 gene. (bvsalud.org)
  • Among candidate genes is the CTLA-4 (cytotoxic T lymphocyte associated) gene located on chromosome 2q33 in humans, which encodes a cell surface molecule providing a negative signal for T cell activation. (bmj.com)
  • Conclusion -The CTLA-4 gene polymorphism is a non-HLA determinant that predisposes to coeliac disease. (bmj.com)
  • CTLA-4 on chromosome 2q33 is a likely candidate gene for autoimmune diseases because of its role in controlling the T cell proliferative response. (bmj.com)
  • The CTLA-4 gene encodes a T lymphocyte surface molecule whose binding to the B7 molecule on antigen presenting cells delivers a negative signal to the T cell and can mediate its apoptosis. (bmj.com)
  • https://maria.stanford.edu/ ), a multimodal recurrent neural network for predicting the likelihood of antigen presentation from a gene of interest in the context of specific HLA class II alleles. (nature.com)
  • We have investigated whether the A49G single nucleotide polymorphism (SNP) genotype of the CTLA-4 gene influenced the development of MS in Southern Australians as well as the interaction of this SNP with the DRB1*15 haplotype. (edu.au)
  • CTLA-4 gene polymorphism in promoter and exon-1 regions in Chinese patients with systemic lupus erythematosus. (semanticscholar.org)
  • Updated analysis of studies on the cytotoxic T-lymphocyte-associated antigen-4 gene A49G polymorphism and Hashimoto's thyroiditis risk. (semanticscholar.org)
  • The activating mutations of the EGFR in a subset of patients with advanced non-small-cell lung cancer (NSCLC) who respond to the EGFR tyrosine kinase inhibitor (TKI) gefitinib or erlotinib are paradigmatic [ 4 ]. (hindawi.com)
  • The absence of CTLA-4 also augments the responder frequency of cytokine-secreting AND TCR + RAG −/− T cells. (pnas.org)
  • By competing for and binding to B7 ligands, CTLA-4 inhibits T cell proliferation and cytokine expansion. (sciencemag.org)
  • In contrast, oral tolerance was intact in chimeras generated using DO11.10xIL-10(-/-) cells, indicating that secretion of this cytokine by antigen-specific cells is not required. (ox.ac.uk)
  • Significantly, the peak mediastinal cytokine production of both IL-5 and IL-4 during CTLA-4 blockade occurred earlier than that in control mice. (nih.gov)
  • Fig. 2 b) but it is interesting that in this lymph node peak cytokine production occurred at the same time in control and anti-CTLA-4- treated mice. (nih.gov)
  • Increased cytokine production from this lymph node reflected increased IL-4 and IL-5 production only as total mesenteric lymph node cell numbers were not significantly different between groups (data not shown). (nih.gov)
  • In addition, one should expect interindividual variations in the autoreactive repertoire of T-cells: some islet-reactive T-cells might already be activated at the time of immunization and their avidities can be expected to vary depending on central (thymic) and peripheral tuning events, which in turn will influence the character (magnitude and cytokine production) of the resulting antigen-specific response. (diabetesjournals.org)
  • The functional impact of anti-CTLA-4 therapy on human immune responses is still unclear. (pnas.org)
  • We therefore suggest that CTLA-4 blockade enhanced NY-ESO-1 antigen-specific B cell and T cell immune responses in patients with durable objective clinical responses and stable disease. (pnas.org)
  • In addition, we further postulated that spontaneous preexisting immune responses to NY-ESO-1 could be augmented by CTLA-4 blockade. (pnas.org)
  • Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical negative regulator of immune responses. (rupress.org)
  • The ability of CTLA-4 blockade to accelerate primary immune responses to a protective level during an acute infection indicates its potential as an immunotherapeutic tool for dealing with infectious agents. (nih.gov)
  • demonstrated that plasmacytoid DCs expressing CCR9 were potent inducers of T reg cell function and suppressed antigen-specific immune responses both in vitro and in vivo. (rupress.org)
  • In July 1994, they presented data at another Gordon Conference showing CTLA-4 inhibited immune responses. (mdanderson.org)
  • It occurred to Allison that the CTLA-4 checkpoint might be shutting down those immune responses and that blocking it might free T cells to more effectively find and kill cancer. (mdanderson.org)
  • The two main outcomes involve the induction or augmentation of beneficial (regulatory) immune responses ( 1 - 3 ) and the elimination (deletion) of deleterious islet-specific effector responses ( 4 - 6 ), both of which are context-dependent and will be discussed below ( Table 1 ). (diabetesjournals.org)
  • In this study, using a T cell-mediated colitis model, we demonstrate that anti-CTLA-4 mAb treatment inhibits T R function in vivo via direct effects on CTLA-4-expressing T R , and not via hyperactivation of colitogenic effector T cells. (jimmunol.org)
  • Although anti-CTLA-4 mAb treatment completely inhibits T R function, it does not reduce T R numbers or their homing to the GALT, suggesting the Ab mediates its function by blockade of a signal required for T R activity. (jimmunol.org)
  • This was confirmed by later work [ 5 , 6 ] showing that CTLA-4 inhibits the initial stage of naïve T cell activation in the lymph nodes. (biomedcentral.com)
  • In Western blots, approximately 25% cross-reactivity with recombinant mouse CTLA-4 is observed. (novusbio.com)
  • Genetic susceptibility to type 1 autoimmune hepatitis is indicated by a preponderance of female subjects and strong associations with human leukocyte antigens (HLA) DRB1*0301 and DRB1*0401. (nih.gov)
  • To determine the frequency and significance of the exon 1 adenine (A)-guanine (G) base-exchange polymorphism for CTLA-4 in patients with type 1 autoimmune hepatitis, 155 northern European Caucasoid patients and 102 ethnically-matched control subjects were tested by polymerase chain reaction. (nih.gov)
  • The CTLA-4 G allele is more common in patients with type 1 autoimmune hepatitis and may represent a second susceptibility allele. (nih.gov)
  • This contribution reports the case of a young female patient with a cytotoxic T-lymphocyte antigen 4 (CTLA-4) heterozygous missense mutation giving rise to a broad range of autoimmune diseases, including central nervous system inflammation presenting as disseminated intramedullary and infiltrating brain lesions on MRI. (muni.cz)
  • Heterozygous germline mutations in CTLA-4 may lead to an autosomal dominant immune dysregulation syndrome with highly variable phenotype, including various immunodeficiency and autoimmune diseases, along with neurological manifestations. (muni.cz)
  • The immune system has inhibitory pathways that maintain self-tolerance and modulate immunity to prevent autoimmune side effects [ 4 ]. (prolekare.cz)
  • However, in its day-to-day activities, CTLA-4 prevents autoimmune targeting of tissues ( 2 ), though the precise mechanism of action and critical controls influencing CTLA-4 function are still emerging. (sciencemag.org)
  • The identification and study of autoimmune diseases has taught us that recognition of self-antigens can have devastating consequences. (diabetesjournals.org)
  • CTLA-4 knockout mice demonstrate an early fatal autoimmune syndrome characterized by lymphoproliferation, (3) while some strains of PD-1 knockout animals develop autoimmunity later in life. (thefreedictionary.com)
  • Particular genotypes of the locus encoding the CTLA-4 glycoprotein have been associated with susceptibility to various autoimmune diseases. (semanticscholar.org)
  • Unraveling the genetic susceptibility to autoimmune thyroid diseases: CTLA-4 takes the stage. (semanticscholar.org)
  • Following vaccination, patients generated weak to no CD4(+) or CD8(+) T-cell response specific to the vaccine antigen but demonstrated increases in effector-memory (CCR7(lo)CD45RA(lo)) tetramer(+)CD8(+) T cells. (nih.gov)
  • The expression of the AND TCR transgene by CD4 + T cells delays but does not prevent the lymphoproliferation in the CTLA-4 −/− mice. (pnas.org)
  • We demonstrate that CTLA-4 regulates the peptide-specific proliferative response generated by naive and previously activated AND TCR + RAG −/− T cells in vitro . (pnas.org)
  • These results demonstrate that CTLA-4 is a key regulator of peptide-specific CD4 + T cell responses and support the model that CTLA-4 plays a differential role in maintaining T cell homeostasis of CD4 + vs. CD8 + T cells. (pnas.org)
  • Peripheral CD4 + T cells are primarily responsible for the lymphoproliferative disorder in CTLA-4 −/− mice expressing an unmanipulated TCR repertoire ( 15 ). (pnas.org)
  • These results suggest that CTLA-4 has differential effects on the CD4 + vs. the CD8 + T cells in vivo . (pnas.org)
  • To test these models and to determine antigenic peptide reactivity of naive T cells in the absence of CTLA-4, we have initiated studies using MHC class I or class II-restricted TCR transgenic CTLA-4 −/− mice. (pnas.org)
  • The role of CTLA-4 in regulating homeostasis and antigen reactivity of CD8 + T cells has been examined in three different MHC class I-restricted TCR transgenic mouse strains ( 21 - 23 ). (pnas.org)
  • CTLA-4 −/− mice expressing MHC class I-restricted TCR transgenes remain healthy for several months but eventually develop a lymphoproliferative disorder, apparently initiated by activation of the normally small population of CD4 + T cells present in these animals ( 22 , 23 ). (pnas.org)
  • The CD8 + TCR transgenic CTLA-4 −/− T cells maintain a naive phenotype in these animals ( 23 , 24 ). (pnas.org)
  • CTLA-4 blockade alone was able to enhance the proliferation only of PD-1 + CTLA-4 + CD8 + TILs and had no effect on CTLA-4 − cells. (aacrjournals.org)
  • However, dual blockade potently enhanced the proliferation of PD-1 + CTLA-4 + CD8 + TILs in response to peptide presented by antigen-presenting cells. (aacrjournals.org)
  • The discovery of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and its role as a key negative regulator for T cells has prompted efforts to target this signaling molecule to improve cancer therapy. (nih.gov)
  • Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a coinhibitory molecule expressed by activated T cells and a subset of regulatory T cells ( 1 - , 4 ). (pnas.org)
  • Polyfunctional T cells, which are able to produce multiple cytokines and chemokines in response to antigen stimulation, have been demonstrated in a number of preclinical models for infectious diseases as well as in patients infected with HIV-1 or immunized using vaccinia constructs ( , 18 ). (pnas.org)
  • In contrast, it has remained more contentious whether CTLA-4 expressed in trans by CD4 + CD25 + Foxp3 + regulatory T cells (T reg cells) has a direct role in their suppressive function. (rupress.org)
  • Constitutive expression of CTLA-4 is a cardinal feature of T reg cells, although the majority of CTLA-4 is found intracellularly in both T reg and conventional T cells, even after activation. (rupress.org)
  • Furthermore, adaptive resistance is gradually developed through the CTLA-4 pathway in Treg cells in larger lymphomas. (aacrjournals.org)
  • CTLA-4 is expressed by a high percentage of these cells, and is often considered as a marker for T R in experimental and clinical analysis. (jimmunol.org)
  • CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance. (ox.ac.uk)
  • We have developed a model using transfer of DO11.10 TCR-transgenic bone marrow into irradiated recipients in which it has been possible to track antigen-specific CD4(+) cells in mesenteric lymph nodes (mLN), Peyer's patches (PP) and lamina propria following primary exposure to antigen. (ox.ac.uk)
  • Investigating the role of CTLA-4 either using anti-CTLA-4 mAb or by generating chimeras using DO11.10xCTLA-4(-/-) mice as donors we have clearly shown that antigen-specific cells require the expression of this regulatory molecule for oral tolerance. (ox.ac.uk)
  • Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a crucial role in negatively regulating T cell responses and has also been implicated in the development and function of natural FOXP3+ regulatory T cells. (tas-102.net)
  • quiescent in the presence of normal (CTLA-4Csufficient) BM-derived cells (22). (tas-102.net)
  • How this regulation occurs has not been decided, but T reg cells have been suggested to be important, especially because T reg cells constitutively express high amounts of CTLA-4. (tas-102.net)
  • CD4+ T reg cells arise in the thymus and have been shown in vitro and in vivo to dominantly inhibit standard T cell responses to both self- and foreign antigens (7). (tas-102.net)
  • As surface appearance of CTLA-4 is discovered on T reg cells in unmanipulated mice generally, one interpretation from the blended BM chimaera data had been that CTLA-4 is certainly primarily 74863-84-6 necessary for T reg cell function and/or maintenance as well as the lymphoproliferation seen in mice is certainly primarily a rsulting consequence faulty T reg cells. (tas-102.net)
  • Though FOXP3+ T reg cells with suppressive activity in vitro could be isolated from mice (unpublished data) (25), 74863-84-6 these are not capable of regulating CTLA-4Cdeficient T cells in vivo clearly. (tas-102.net)
  • Although the function of T reg cells in managing autoreactive T cells in steady-state circumstances is not directly addressed, several reports have looked into the in vivo relevance of CTLA-4 on T reg cells through an induced colitis model (26C28). (tas-102.net)
  • CTLA-4 on effector T cells or T regs) within this model was unidentified, it's been proven that CTLA-4 blockade variably disrupts the control of colitogenic B7-deficient (T cells by WT (CTLA-4+) T reg cells (30), recommending that CTLA-4 on T reg cells is pertinent for initiating and/or preserving regulation functionally. (tas-102.net)
  • However, the problem continued to be uncertain because tests using Ab-mediated blockade of CTLA-4 possess provided inconsistent leads to the same model program, and T reg cells from mice are also reported to avoid the progression of colitis (30). (tas-102.net)
  • Given the contrasting observation in mice where endogenous T reg cells cannot regulate lymphoproliferation of T cells, it is obvious that the requirements for regulation may be very unique between the colitis model and CTLA-4 deficiency. (tas-102.net)
  • In this study, we use mixed stem cell chimaeras and T cell transfer systems to define the cellular and molecular mechanisms involved in trans-regulation of CTLA-4Cdeficient T cells. (tas-102.net)
  • Collectively, these results demonstrate that T reg cells can dominantly control a large pool of self-reactive T Rabbit Polyclonal to SLC30A4 cells in vivo and that CTLA-4 is vital because of their cell function. (tas-102.net)
  • Outcomes CTLA-4Csufficient blastocyst and BM-derived cells stably regulate T cells in vivo mice develop substantial lymphoproliferation and a multi-organ inflammatory response powered by self-antigen particular T cells (10, 11). (tas-102.net)
  • Peripheral T cells are turned on by 4 d old detectably, and transfer of T cells from mice to lymphopenic hosts such as for example mice recapitulates the condition (spending and lymphoproliferation), highlighting the autoaggressive character of T cells (unpublished data). (tas-102.net)
  • Values represent the mean concentration of IL-5 produced from 1 × 106 cells from 4 mice and adjusted to IL-5 production per lymph node based on the total lymph node cell number. (nih.gov)
  • CTLA-4 is a negative immune regulator essential for the function of regulatory T-cells, themselves responsible for maintaining self-tolerance and immune homeostasis. (muni.cz)
  • CTLA-4 is a key molecule expressed on the surface of T cells. (prolekare.cz)
  • Several of the identified T-cell epitopes share similarity with common bacterial and viral antigens, suggesting the involvement of pre-existing microbial cross-reactive T cells in rapid and durable tumour regression seen in some patients. (bireme.br)
  • Although there are several immune checkpoint pathways that regulate immune cells, to date, the two major approaches to immune checkpoint blockade that have been investigated clinically have targeted cytotoxic-T-lymphocyte antigen (CTLA-4) and the programmed cell death pathway. (aspetjournals.org)
  • Cytotoxic T lymphocyte antigen-4 (CTLA-4) operates the earliest checkpoint controlling whether or not T cells respond to antigen. (sciencemag.org)
  • CD1 molecules, like MHC I and II, play an equally important role in the immune system by presenting lipid, glycolipid and lipopeptide antigen to T and NKT cells. (novusbio.com)
  • Validation of the expression of human CTLA-4 by Raji-hCTLA4 cells. (invivogen.com)
  • CTLA-4 is transiently expressed by activated T cells and is not detectable in resting T cells. (beckman.com)
  • Prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and is likely an important therapeutic target for the treatment of prostate carcinoma. (springermedizin.de)
  • Arndt C, Feldmann A, Koristka S, Cartellieri M, Dimmel M, Ehninger A, Ehninger G, Bachmann M (2014) Simultaneous targeting of prostate stem cell antigen and prostate-specific membrane antigen improves the killing of prostate cancer cells using a novel modular T cell-retargeting system. (springermedizin.de)
  • This enables the T cells to eliminate cells with "foreign" or "abnormal" antigens without harming the normal cells. (wikipedia.org)
  • Any somatic mutation has a probability of producing a new antigen that can be recognized by T cells. (wikipedia.org)
  • A class of genes, named cancer-germline genes, is expressed in a large variety of cancer cells but not in normal cells, with the exception of germline cells, which do not carry MHC molecules on their surface and therefore do not present the antigens. (wikipedia.org)
  • When bound to antigen-presenting cells, it acts as an off switch. (prospecbio.com)
  • Furthermore, a decrease in the expression of CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4) was described in these cells, both in the surface membrane and intracellularly (8). (thefreedictionary.com)
  • Malignant cells may also express ligands for the immune checkpoint CTLA-4 (cytotoxic T lymphocyte antigen 4) and PD-1 (programmed cell death 1), present on the surface of activated T lymphocytes, inhibiting their functions [14-19]. (thefreedictionary.com)
  • CTLA-4 is a coinhibitory molecule that is induced on activated T cells. (wikipedia.org)
  • Regulatory T cells produce CTLA-4. (wikipedia.org)
  • Examples of negative checkpoint regulators include CTLA-4, PD-1 and VISTA expressed on T-cells. (medindia.net)
  • 2-4% of circulating CD4+ T cells) (1,2). (biocare.net)
  • Overall, NY-ESO-1-specific T cell responses increased in frequency and functionality during anti-CTLA-4 treatment, revealing a polyfunctional response pattern of IFN-γ, MIP-1β and TNF-α. (pnas.org)
  • We summarize here recent findings that suggest a previously unrecognized role for CTLA-4 in the regulation of T cell responses. (nih.gov)
  • Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blockade can promote antitumor T cell immunity and clinical responses. (sciencemag.org)
  • This study provides direct evidence that CTLA-4 has a specific, nonredundant role in the function of normal T R . This role has to be taken into account when targeting CTLA-4 for therapeutic purposes, as such a strategy will not only boost effector T cell responses, but might also break T R -mediated self-tolerance. (jimmunol.org)
  • Indeed, a breakdown in intestinal homeostasis and the development of aberrant inflammatory responses to intestinal bacteria have been associated with the pathogenesis of inflammatory bowel disease (IBD) 3 in humans ( 3 , 4 ). (jimmunol.org)
  • PD-1/PD-L1, CTLA-4) has been shown to achieve profound responses in several of solid cancers. (hindawi.com)
  • Antitumor responses, including durable complete regression of disease, have been observed in ∼10% of patients who receive anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapy. (aacrjournals.org)
  • genetic susceptibility, immune mediated with loss of tolerance to self-antigen (pyruvate dehydrogenase complex), defective bicarbonate umbrella. (medscape.com)
  • Clinical associations of the genetic variants of CTLA-4, Tg, TSHR, PTPN22, PTPN12 and FCRL3 in patients with Graves' disease. (semanticscholar.org)
  • In addition, the critical role of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) molecule in maintaining self-tolerance has been established. (biomedsearch.com)
  • Cytotoxic T lymphocyte associated antigen (CTLA-4) blockade is being explored in numerous clinical trials as an immune-based therapy for different malignancies. (aacrjournals.org)
  • Cytotoxic T lymphocyte associated antigen (CTLA-4) plays a critical role in the regulation of T-cell activation ( 1 - 4 ). (aacrjournals.org)
  • Here, we review the various biological pathways and emerging biomarkers implicated in response to PD-(L)1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) therapies, including oncogenic signaling pathways, human leukocyte antigen (HLA) variability, mutation and neoantigen burden, microbiome composition, endogenous retroviruses (ERV), and deficiencies in chromatin remodeling and DNA damage repair (DDR) machinery. (biomedcentral.com)
  • Cytotoxic T lymphocyte antigen-4 ( CTLA-4 ) is an important immunoregulatory molecule that plays a role in the maintenance of T cell homeostasis. (thefreedictionary.com)
  • Variants of cytotoxic T-lymphocyte antigen 4 (CTLA-4) with high affinity, potency and stability. (patents.com)
  • CTLA-4 inhibitors prevent competitive inhibitory binding of CTLA-4 with B7 ligands, which allows for more effective T cell activation. (biomedcentral.com)
  • 4 - 6 In addition, patients may lose the therapeutic window to gain substantial benefit from each drug that has been proven to provide overall survival gains. (dovepress.com)
  • These data provide an immunologic rationale for the efficacy of anti-CTLA-4 therapy and call for immunotherapeutic designs that combine NY-ESO-1 vaccination with CTLA-4 blockade. (pnas.org)
  • Whether it directly contributes to disease susceptibility or represents a marker for a locus in linkage disequilibrium with CTLA-4 needs further investigation. (bmj.com)
  • CTLA-4 -1722T/C polymorphism and systemic lupus erythematosus susceptibility: a meta-analysis involving ten separate studies. (semanticscholar.org)
  • However, single and combination therapies targeting TIM-3, CTLA-4, and/or PD-L1 failed to reverse susceptibility to secondary infection. (asm.org)
  • Prior clinical trials reported adverse events associated with anti-CTLA-4 therapy consisting of tissue-specific inflammatory conditions termed immune-related adverse events (irAE), which have included dermatitis, hepatitis, colitis, pancreatitis, hypophysitis, inflammatory myopathy, and uveitis ( 16 - 19 ). (aacrjournals.org)
  • Clinical trials testing the combination of PD-(L)1 or CTLA-4 blockade with molecular mediators of these pathways are becoming more common and may hold promise for improving treatment efficacy and response. (biomedcentral.com)
  • Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4 Blockade. (broadinstitute.org)
  • After the initial studies showing the effects of CTLA-4 and PD-1 blockade, the clinical development has been dramatic. (thefreedictionary.com)
  • High clinical suspicion, timely evaluation and multi-disciplinary management provide the foundation for optimal clinical outcomes 4 . (caep.ca)
  • Antigen presentation profiling reveals recognition of lymphoma immunoglobulin neoantigens. (nature.com)
  • The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. (creative-biolabs.com)
  • In other instances, the normal peptide is presented at the cell surface and consequently the T lymphocytes that recognize the antigen have been eliminated by the central tolerance process that occurs in the thymus. (wikipedia.org)
  • NY-ESO-1 is a cancer/testis antigen that is expressed in a variety of human malignancies but not in normal tissues except for the testis and placenta ( 15 ). (pnas.org)
  • Western blot shows lysates of NS0 mouse myeloma cell line either mock transfected or transfected with human CTLA-4. (novusbio.com)
  • Detects human CTLA-4 in direct ELISAs and Western blots. (novusbio.com)
  • Accurate prediction of antigen presentation by human leukocyte antigen (HLA) class II molecules would be valuable for vaccine development and cancer immunotherapies. (nature.com)
  • Human leukocyte antigen shared epitope (HLA-SE) genotyping was performed at high resolution. (harvard.edu)
  • Human CTLA-4 expression has been verified by flow-cytometry. (invivogen.com)
  • The Human CTLA-4 ELISA Kit (Colorimetric) measures human CTLA-4 in cell culture supernatant, serum, plasma (edta, heparin). (fishersci.com)
  • CTLA-4 has been shown to play a role in human diseases (1). (biocare.net)
  • CTLA-4-deficient mice develop a fatal lymphoproliferative disorder, characterized by polyclonal expansion of peripheral lymphocytes. (pnas.org)
  • CTLA-4-deficient mice die at 3-4 weeks of age as a result of a lymphoproliferative disorder caused by polyclonal T cell expansion ( 12 - 14 ). (pnas.org)
  • Based on the phenotype of the CTLA-4 −/− mice, we proposed ( 15 , 16 ) that CTLA-4 may provide an inhibitory signal that prevents CD4 + T cell activation during the continuous interaction of TCR and MHC that is shown to be required for T cell survival ( 17 - 21 ). (pnas.org)
  • In contrast to the striking effect of the Ab, CTLA-4-deficient mice can produce functional T R , suggesting that under some circumstances other immune regulatory mechanisms, including the production of IL-10, are able to compensate for the loss of the CTLA-4-mediated pathway. (jimmunol.org)
  • C57BL/6 mice were inoculated i.p. with 1,000 Nb L3 larvae and treated with control hamster IgG (open squares) or hamster anti-mouse CTLA-4 mAb (filled squares) at 1 mg/week beginning at day 0. (nih.gov)
  • To establish whether T cell effector function is altered by blockade of CTLA-4 signaling, we followed IL-4 and IL-5 production in the draining mediastinal and mesenteric lymph nodes of mice infected with Nb and receiving weekly injections of anti-CTLA-4 neutralizing mAb. (nih.gov)
  • The mediastinal lymph node obtained from mice given anti-CTLA-4 mAb had nearly fourfold more lymphocytes 6 d after infection than control mice (Fig. 3). (nih.gov)
  • In the study, Trianni humanized mice were separately immunized with PD-1 and CTLA-4 using four immunization protocols. (prnewswire.com)