CTLA-4 blockade Therapies

Cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) is the prototypic immune checkpoint receptor, which play a major role in downregulation of the immune response. Expressed exclusively on T cells, CTLA-4(CD152) primarily acts to antagonize signaling of CD28, the typical second activating signal in T cells. CTLA4 transmits an inhibitory signal to thwart early T cell activation, whereas CD28 transmits a stimulatory signal for T cell proliferation and activation. T-cell expression of CTLA-4 indirectly facilitates tumor progression by restraining host antitumoral immunity. In contrast, administration of a monoclonal antibody to block CTLA-4 function can alleviate restraints on T-cell activity to promote immune-mediated tumor regression.
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