antiCTLA4

Anti-CTLA-4 refers to monoclonal antibodies that bind to the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), blocking its interaction with ligands CD80/CD86 on antigen-presenting cells, thereby altering T cell activation.

CTLA-4 normally dampens early T cell activation; it outcompetes CD28 for B7 ligands and transmits inhibitory signals. Blocking CTLA-4 shifts balance toward T cell activation, enhancing anti-tumor immune responses, particularly in lymph nodes during T cell priming. Effects on regulatory T cells may contribute to activity.

The best-known anti-CTLA-4 antibodies are ipilimumab, approved for metastatic melanoma and later tested in other cancers; tremelimumab has been studied but not approved broadly. In cancer therapy, anti-CTLA-4 is sometimes used in combination with anti-PD-1/PD-L1 therapies to improve response rates, though with higher rates of immune-related adverse events.

Common adverse events include colitis, dermatitis, hepatitis, endocrinopathies, and other irAEs; management involves monitoring and immunosuppression with corticosteroids or other agents, with dose interruption or discontinuation for severe events. Efficacy varies by tumor type and patient.

History: CTLA-4 was identified as a negative regulator of T cell activation in the late 1980s, leading to the development of checkpoint inhibitors in the 2000s; ipilimumab became the first FDA-approved immune checkpoint inhibitor in 2011. Ongoing research explores biomarkers and combination regimens to optimize benefit and minimize toxicity.