Toxicity associated with antibody-drug conjugates and corresponding research strategies
刘连奇 1肖典 1钟武 1周辛波 1李松1
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作者信息
1. 军事医学研究院国家应急防控药物工程技术研究中心,北京 100850
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摘要
目的 探讨新兴抗肿瘤药物抗体偶联药物(antibody drug conjugate,ADC)的毒性、毒性诱发原因以及避免毒性的研究对策,以期为下一代新型高效低毒ADC研发提供参考.方法 分析整理近年来已上市以及处于临床阶段的ADC毒性数据,从ADC结构入手,理清ADC结构与毒性产生的关系,参考现阶段避免毒性的有效对策,寻找下一代高效低毒ADC的发展方向.结果及结论 针对ADC研发的不同阶段,提供避免毒性的研究对策,其中ADC源头设计理念的更新是解决ADC毒性的关键.
Abstract
Objective To explore the toxicity,causes of toxicity,and strategies to minimize toxicity of antibody-drug conjugates(ADCs),an emerging class of anticancer therapeutics,in order to provide reference for the development of the next generation of ADCs with high efficacy and low toxicity.Methods The data on toxicity of ADCs that had been marketed and were in clinical trials was summarized and analyzed.By focusing on the structure of ADCs,the relationship between structure of ADCs and generated toxicities was revealed.By referring to effective strategies for minimizing toxicities in place,the future developments of the next generation of ADCs with high efficacy and low toxicity were predicted.Results and Conclusion Research strategies for preventing toxicities are provided for different stages of ADC development.Among them,updated and core concepts of the design of ADCs are crucial to addressing the toxicities of ADCs.
关键词
抗体偶联药物/抗肿瘤/效应分子/毒性/安全性
Key words
antibody drug conjugate/antitumor/payloads/toxicity/safety
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