Tremelimumab (CP-675,206), a Cytotoxic T Lymphocyte–Associated Antigen 4 Blocking Monoclonal Antibody in Clinical Development for Patients with Cancer
| Autor: | Douglas C. Hanson, Antoni Ribas, Robert Millham, Paul C. Canniff, Dennis Noe, Steven H. Bernstein, Jesus Gomez-Navarro, Deborah Jean Guyot, Amarnath Sharma |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Immunoconjugates T cell Dacarbazine Drug Evaluation Preclinical Antibodies Monoclonal Humanized Abatacept Clinical Trials Phase II as Topic Antigen Antigens CD medicine Humans Cytotoxic T cell CTLA-4 Antigen Melanoma business.industry Antibodies Monoclonal medicine.disease Antigens Differentiation Cytokine release syndrome medicine.anatomical_structure Clinical Trials Phase III as Topic Oncology CTLA-4 Immunology Cancer research business Tremelimumab Immunosuppressive Agents medicine.drug |
| Zdroj: | The Oncologist. 12:873-883 |
| ISSN: | 1549-490X 1083-7159 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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