The monoclonal antibody to cytotoxic T lymphocyte antigen 4, ipilimumab, in the treatment of melanoma

Claire Verschraegen
Professor of Medicine, Division of Hematology Oncology, University of Vermont, Vermont Cancer Center, VT, USA

Background: Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an inhibitory regulator of the T-cell immune response against tumor cells. Ipilimumab is a monoclonal antibody directed against CTLA-4.
Objective: This review describes the basic mechanism of ipilimumab and discusses data available to date with regards to its safety and efficacy profile.
Methods: Data from clinical trials including abstracts was reviewed using the PubMed Database, as well as the American Society of Clinical Oncology Abstract Database.
Conclusion: CTLA-4 inhibition with a monoclonal antibody is usually well tolerated and has efficacy as a therapeutic agent in a variety of cancers. The classical response interpretation has changed because of the delayed mechanism of action. The toxicities are autoimmune events and guidelines for treatment of these effects are discussed. Therapy with ipilimumab leads to durable responses. The first two Phase III randomized studies showed an improvement of survival at 1, 2, and 3 years. Other studies are currently underway to better understand the optimal treatment administration of ipilimumab in melanoma.

Keywords: melanoma, CTLA-4, ipilimumab, immune-related adverse events, melanoma, modified immune response criteria