CTLA-4

Class

Anti-CTLA-4 monoclonal antibody (recombinant humanized IgG1, ADCC-enhanced)

Pathway

T-cell checkpoint blockade plus CD28 co-stimulation enhancement

CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) is an inhibitory receptor expressed on activated T cells and constitutively on regulatory T cells. It competes with the co-stimulatory receptor CD28 for the same ligands, CD80 and CD86, on antigen-presenting cells. Because CD28 engagement is required to fully activate a T cell after its receptor recognizes antigen, CTLA-4 acts as a brake early in the immune response, limiting how vigorously T cells expand and attack. Antibodies that block CTLA-4 remove this brake, allowing broader and more sustained T-cell activation. This mechanism is central to cancer immunotherapy, where the goal is to unleash immune recognition of tumor cells that would otherwise evade destruction. Some antibodies in this class are engineered with enhanced antibody-dependent cellular cytotoxicity (ADCC), a property that allows them to selectively eliminate CTLA-4-high regulatory T cells within tumors, in addition to simply blocking the receptor. This dual action—checkpoint blockade plus regulatory T-cell depletion—aims to shift the balance further toward antitumor immunity. Because CTLA-4 blockade acts upstream in T-cell priming, its effects are broader and more systemic than checkpoint mechanisms acting later, such as PD-1 blockade, which has implications for both efficacy and toxicity.