Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer: evidence for the activation of humoral and cellular antitumor immunity
| Autor: | Christopher F. Nicodemus, B. C. Schultes, J. M. Cermak, Sun Young Rha, Anthony W. Tolcher, Eric K. Rowinsky, Lisa A. Hammond, S. Gail Eckhardt, Theresa L. Whiteside, J. Stephenson, P. Monroe, J. S. de Bono |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Cellular immunity medicine.drug_class Monoclonal antibody Metastasis Mice Immune system Immunity Neoplasms medicine Animals Humans Neoplasm Metastasis neoplasms Aged Immunity Cellular biology business.industry Carcinoma Mucin-1 Cancer Antibodies Monoclonal Hematology Middle Aged medicine.disease digestive system diseases Oncology Immunology Humoral immunity Antibody Formation biology.protein Female Antibody business |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology. 15(12) |
| ISSN: | 0923-7534 |
| Popis: | Background: BrevaRex w mAb-AR20.5 is a murine anti-MUC1 monoclonal antibody generated to induce MUC1 antigen-specific immune responses through the formation of immune complexes with circulating MUC1 and/or MUC1-expressing tumor cells that may target these immune complexes (IC) to receptors on dendritic cells (DCs). Patients and methods: A phase I study focusing on safety and immunology evaluated 1, 2 and 4-mg doses. Seventeen patients with MUC1-positive cancers received intravenous infusions of the antibody over 30 min on weeks 1, 3, 5, 9, 13 and 17 of treatment. Results: mAb-AR20.5 was well-tolerated, not associated with dose-limiting toxicity, and did not induce hypersensitivity reactions. Overall, five of 15 evaluable patients developed human anti-mouse antibodies (HAMA), five developed anti-idiotypic antibodies (Ab2) and seven developed anti-MUC1 antibodies. Immune responses were most prominent in the 2-mg dose cohort for all parameters tested, and treatment-emergent MUC1-specific T-cell responses were detected in five of 10 evaluable patients treated with mAb-AR20.5. Conclusions: The injection of a murine antibody to MUC1 induces MUC1-specific immune responses in advanced cancer patients. Anti-MUC1 antibody increases correlated with decrease or stabilization of CA15.3 levels (P = 0.03). The 2-mg dose of mAb-AR20.5 showed strongest biological activity, and will be evaluated in future efficacy trials. |
| Databáze: | OpenAIRE |
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