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CTLA-04 0,5 ml

BC-ACI3211B
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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. CTLA-4 exhibits cell surface and intracellular constitutive expression on memory T-cells and at a low level by T-regulatory cells (Tregs; 2-4% of circulating CD4+ T cells) (1,2). CTLA-4 primarily inactivates T-cell activity by competing with the CD28 costimulatory molecule (3). CD28 and CTLA-4 share the identical ligands of CD80 and CD86 on antigen-presenting cells; and thus CTLA-4 competes with CD28 function in T-cell survival, proliferation, and recruitment (3,4). In particular, CTLA-4 down-modulates CD4+ helper T-cell activity and enhances Treg immunosuppressive functions (5,6).

CTLA-4 has been shown to play a role in human diseases (1). CTLA-4 acts as a physiological brake on the activated immune system in order to maintain immune homeostasis. Several suppressive mechanisms for T-cell functions have been attributed to CTLA-4. 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). Another CTLA-4 inhibitor, tremelimumab (IgG2 isotype), has also proven successful in metastatic melanoma and other malignancies (1,7).

 

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