University of New Mexico Cancer Research and Treatment Center, Division of Hematology Oncology, Albuquerque, NM 87131, USA.
BACKGROUND: Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an inhibitory regulator of the T cell immune response against tumor cells. Ipilimumab (MDX-010) is a monoclonal antibody directed against CTLA-4. OBJECTIVE: To describe the basic mechanism of ipilimumab and discuss data available to date with regards to its safety and efficacy profile. METHODS: Data from clinical trials including abstracts were reviewed using the PubMed Database as well as the American Society of Clinical Oncology Abstract Database. CONCLUSIONS: CTLA-4 inhibition with a monoclonal antibody is usually well tolerated and has efficacy as a therapeutic agent in a variety of cancers. The most clinically important toxicities have been related to autoimmune events, and guidelines for treatment of these effects are now available. Preliminary results indicate that therapy with ipilimumab leads to durable responses. Pharmacokinetics and pharmacodynamics are different from those of traditional chemotherapy agents. Phase III studies are currently underway for melanoma.