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The Oncologist, Vol. 12, No. 7, 873-883, July 2007; doi:10.1634/theoncologist.12-7-873
© 2007 AlphaMed Press

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Tremelimumab (CP-675,206), a Cytotoxic T Lymphocyte–Associated Antigen 4 Bl...
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Melanoma and Cutaneous Malignancies

Tremelimumab (CP-675,206), a Cytotoxic T Lymphocyte–Associated Antigen 4 Blocking Monoclonal Antibody in Clinical Development for Patients with Cancer

Antoni Ribasa,c, Douglas C. Hansond, Dennis A. Noee, Robert Millhamf, Deborah J. Guyotg, Steven H. Bernsteinh, Paul C. Canniffd, Amarnath Sharmae, Jesus Gomez-Navarrof

aDepartment of Medicine, Division of Hematology/Oncology, bDepartment of Surgery, Division of Surgical Oncology, and cJonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, California, USA; Departments of dImmunology, eClinical PK/PD, gDrug Safety R&D, and fClinical Oncology, Pfizer Global Research & Development, Groton-New London, Connecticut, USA; hUniversity of Rochester School of Medicine and Dentistry, Rochester, New York, USA

Key Words. CTLA-4 • Melanoma • T cell • Antitumor

Correspondence: Correspondence: Jesus Gomez-Navarro, M.D., Pfizer Global Research & Development, Groton-New London, Connecticut 06340, USA. Telephone: 860-732-2079; Fax: 860-732-7127; e-mail: jesus.gomez-navarro{at}pfizer.com

Tremelimumab (CP-675,206) is a fully human monoclonal antibody specific for human cytotoxic T lymphocyte–associated antigen 4 (CTLA-4, CD152) in clinical development for patients with cancer. Blocking the CTLA-4 negative costimulatory receptor with the antagonistic antibody tremelimumab results in immune activation. Administration of tremelimumab to patients with locally advanced and metastatic melanoma has resulted in a subset of patients with durable objective tumor regressions. Its IgG2 isotype minimizes the possibility of cytotoxic effects on activated T lymphocytes and cytokine release syndrome. Preclinical testing in vitro and in large animal models predicted the target concentrations of circulating antibody in humans necessary for a pharmacodynamic effect. Phase I clinical trials provided evidence of dose- or exposure-related effects consistent with the anticipated mechanism of action. Further clinical development has led to two ongoing registration trials in patients with metastatic melanoma: a phase III randomized trial of tremelimumab versus dacarbazine or temozolomide in previously untreated patients with advanced melanoma and a phase II trial of tremelimumab in previously treated patients with advanced melanoma.

Disclosure of potential conflicts of interest is found at the end of this article.




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