What is the role of cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma?
With increasing knowledge of the molecular basis of the immune system and mechanisms of tumor tolerance, novel approaches to treating malignant diseases refractory to standard therapies are being investigated. Monoclonal antibodies (mAbs) that bind cytotoxic T lymphocyte-associated antigen (CTLA)-4 can block inhibitory signals normally generated through this receptor, thus prolonging and sustaining T-cell activation and proliferation. These antibodies are being developed and tested in patients with metastatic melanoma. This article reviews data published or presented at scientific congresses describing the clinical safety and antitumor activity of two different anti-CTLA-4 mAbs: tremelimumab (CP-675,206) and ipilimumab (MDX-010). Overall, although the response rate has not been consistently higher than the response rates associated with other treatments, the induction of durable responses and the favorable safety profile observed with anti-CTLA-4 mAbs are encouraging. However, the true advantage of these new drugs may depend largely on the characterization of predictive biomarkers of activity and subsequent targeting of responsive patients.
Robert
Caroline
C
Institute Gustave Roussy, 94805 Villejuif Cedex, France. caroline.robert@igr.fr
Ghiringhelli
Francois
F
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology*; D060908:CTLA-4 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab; C520704:tremelimumab