Monoclonal Antibodies Targeting the CTLA-4 Checkpoint

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MONOCLONAL ANTIBODIES TARGETING THE CTLA-4 CHECKPOINT

CTLA-4 is a protein found on the surface of T cells. CTLA-4 normally acts as a type of "off switch" within activated T cells that helps keep the activity of the T cells in check, preventing expansion of T cells within the body.

In the setting of cancer, this can stop T cells from attacking cancer cells. Thus, it was hypothesized that blockade of CTLA-4 signaling might increase the effectiveness of antitumor immune responses. Monoclonal antibodies were subsequently developed that attach to CTLA-4 on T cells and prevent it from binding to its ligand, CD80, on antigen-presenting cells, as shown in the animation below.

When anti-CTLA-4 antibodies are received, the expansion of T-cell responses is theoretically no longer inhibited following antigen presentation in lymphoid organs (or in the periphery). This promotes the production of activated T cells, including tumor-specific T cells. This increases the adaptive immune response against tumor cells.