抗体药物偶联物临床前安全性评价策略

Strategy of antibody-drug conjugates in preclinical safety evaluation

抗体药物偶联物(ADC)是近年来肿瘤治疗研究中的热点问题。临床上ADC药物在增强药效作用的同时,还极大减小毒副作用,因而前景良好。但该类药物组成相对复杂,且临床前安评经验积累较少,为安评带来挑战。本文通过分析ADC药物的作用方式、主要的毒性风险和临床前/临床试验中常见毒性,同时研究已批准ADC药物毒性试验,结合ICH S6(生物技术药物临床前安全性评价)和ICH S9(抗肿瘤药物研究及评价)指导原则,探讨ADC药物的临床前安评策略。

Recently,increasing cancer researches focus on antibody-drug conjugates（ADCs）which can improve the anti-tumor potency with less adverse effect while benefiting patients in the future. However,safety evaluation of ADCs is a big challenge because of complex components as well as in experience in preclinical studies. In this review,the authors reviewed the mode of action,hazard risks,and toxicity observed in preclinical/clinical studies of ADCs,summarized the preclinical studies of Adcetris（brentuximab vedotin）and Kadcyla（ado-trastuzumab emtansine）,and suggested a better strategy of ADCs in preclinical safety evaluation.