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[摘要]：Early clinical development in the field of targeted delivery of cytotoxic drugs to tumors using antibodies failed to achieve effective, well-tolerated anticancer products. In recent years, several new highly potent cell-killing agents, such as thiol derivatives of the potent antimitotic micro tubule agent maytansine, developed by ImmunoGen, are being utilized to make a new generation of antibody-drug conjugates (ADCs). Several antibody-maytansinoid conjugates (AMCs) have shown encouraging efficacy in clinical trials, including trastuzumab-DM1 (T-DM1), which targets HER2(+) breast cancer, SAR-3419, which targets CD19 expressed on B-cell malignancies, and IMGN-901, which targets CD56 expressed on both solid tumors (small cell lung cancer and other neuroendocrine tumor types) and hematological tumors, including multiple myeloma. Besides their demonstrated efficacy in phase I and/or phase II clinical studies, these AMCs are well tolerated, with no clinically significant myelosuppression, suggesting that AMC compounds are well suited for evaluation in combination treatment regimens. Maytansinoids are payloads for antibody-mediated delivery that are realizing the promise of ADCs for improved targeted therapy in cancer patients. |
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