Monoclonal Antibodies to CTLA-4 with Focus on Ipilimumab

Abstract

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4 or CD152) is a negative regulator of T-cell mediated immune responses, which plays a critical role in suppressing autoimmunity and maintaining immune homeostasis. Because of its inhibitory activity on T cells, CTLA-4 has been investigated as a drug target to induce immunostimulation, blocking the interaction with its ligands. The antitumour effects mediated by CTLA-4 blockade have been attributed to a sustained active immune response against cancer cells, due to the release of a brake on T cell activation. Ipilimumab (Yervoy, Bristol–Myers Squibb) is a fully human monoclonal IgG1κ antibody against CTLA-4 approved by FDA and EMA in 2011 for the treatment of advanced (unresectable or metastatic) melanoma, based on the increase of overall survival demonstrated in a phase III clinical trial. Further development of ipilimumab includes its use in other refractory and advanced solid tumours, either as monotherapy or in combination with additional immunostimulating agents or molecularly targeted therapies.KeywordsIpilimumabImmunotherapyCancer