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Tremelimumab (CP-675,206), a cytotoxic T lymphocyte associated antigen 4 blocking monoclonal antibody in clinical development for patients with cancer Ribas A; Hanson DC; Noe DA; Millham R; Guyot DJ; Bernstein SH; Canniff PC; Sharma A; Gomez-Navarro JOncologist 2007[Jul]; 12 (7): 873-83Tremelimumab (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 IgG(2) 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.|Abatacept[MESH]|Antibodies, Monoclonal, Humanized[MESH]|Antibodies, Monoclonal/*therapeutic use[MESH]|Antigens, CD/*therapeutic use[MESH]|Antigens, Differentiation/*therapeutic use[MESH]|CTLA-4 Antigen[MESH]|Clinical Trials, Phase II as Topic[MESH]|Clinical Trials, Phase III as Topic[MESH]|Drug Evaluation, Preclinical[MESH]|Humans[MESH]|Immunoconjugates/*therapeutic use[MESH]|Immunosuppressive Agents/*therapeutic use[MESH]|Melanoma/*drug therapy/immunology[MESH] |
