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Moving forward with immunotherapy: the rationale for anti-CTLA-4 therapy in melanoma
Division of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a molecule mobilized to the T-cell surface following activation, resulting in physiologic control of the immune response, to avoid damage from excess T-cell activation and to prevent autoimmunity. CTLA-4 blockade with monoclonal antibodies unblocks this physiologic suppression of cytotoxic T-cell–mediated immune responses and may enhance the immune response against malignant cells. Two fully human anti-CTLA-4 monoclonal antibodies (ipilimumab and tremelimumab) are being investigated for advanced melanoma and other malignancies. Results from early clinical trials demonstrated efficacy and tolerability when these antibodies are used alone or in combination with other agents in several tumor types. However, emerging data suggest that anti-CTLA-4 therapy is different from “traditional,” nonspecific immunotherapies for melanoma (interferon-a and interleukin-2) in terms of kinetics, type, and duration of response and adverse-event profile, specifically immune-related adverse events. Ongoing and future efforts to develop CTLA-4 antibody-based regimens must consider the unique characteristics of these therapeutic agents.
| Commun Oncol 2008;5:367–374 | full text |  154 kb |