期刊
JOURNAL OF IMMUNOTHERAPY
卷 30, 期 4, 页码 455-467出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0b013e31803bb421
关键词
HER2/neu; bispecific antibody; immunization
资金
- NCI NIH HHS [CA21115, CA14958, CA-23318, CA50633, CA58262, CA23318, CA27525, CA66636] Funding Source: Medline
2B1 is a bispecific murine monoclonal antibody that binds to the extracellular domains of HER2/neu and Fc gamma RIII. 2BI efficiently promotes the lysis of tumor cells overexpressing HER2/neu by natural killer cells and mononuclear phagocytes that express the Fc gamma RIII A isoform. Here, we report the results of E3194, a phase 1B/2 trial conducted by the Eastern Cooperative Oncology Group that employed 2BI therapy in 20 women with metastatic breast cancer. The median age was 51 years. All but I patient had received prior chemotherapy. After the first dose, 3 of the initial 8 patients experienced dose-limiting toxicities that required dose-reduction. The nature of these dose-limiting toxicities resulted in a reduced dose from 2.5 mg/m(2)/d to 1 mg/m(2)/d in the remaining 12 patients. Objective antitumor responses were not seen. However, 2B1 therapy induced adaptive immune responses to both intracellular and extracellular domains of HER2/neu. Even though 2B1 antibody therapy did not show activity in metastatic breast cancer at the current administered doses, the ability of this antibody to induce detectable immune responses against an important tumor antigen has implications for understanding the mechanisms by which antibodies that mediate anti body-directed cellular cytotoxicity may exert their clinical antitumor effects.
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