抗体偶联药物的相关毒性和研究对策

doi:10.19803/j.1672-8629.20240356

中国药物警戒 ›› 2024, Vol. 21 ›› Issue (7): 721-729.
DOI: 10.19803/j.1672-8629.20240356

抗体偶联药物的相关毒性和研究对策

刘连奇, 肖典, 钟武, 周辛波^#, 李松^*

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

收稿日期:2024-05-27 出版日期:2024-07-15 发布日期:2024-07-31
通讯作者: ^* 李松,男,研究员,中国工程院院士,新药设计与合成。李松,中国工程院院士,现任中国药学会副理事长、军事科学院军事医学研究院研究员。领衔获得国家科技进步奖一等奖2项,国家技术发明二等奖1项、省部级科技进步奖6项。长期从事药物分子设计和合成研究,率先开展计算机辅助药物大规模筛选新技术新方法研究。建立了我国自主防控流感大流行药物的国家能力储备生产线,并出色完成了国家抗流感药品战略储备任务,建成了我军第一个军用特需药物中试基地和高效发现平台。主持研发了5个新药,在国家战略性药物和军队特需药物的研究中做出突出贡献。获国家新药证书10项,军队特需新药证书4项。以第一发明人获得中国、美国、欧盟、日本等国发明专利授权110项。发表研究论文100余篇。E-mail：lis.lisong@gmail.com;^#为共同通信作者。
作者简介:刘连奇,男,助理研究员,新药设计与合成。
基金资助:
国家自然科学基金资助项目（L2324220）

Toxicity associated with antibody-drug conjugates and corresponding research strategies

LIU Lianqi, XIAO Dian, ZHONG Wu, ZHOU Xinbo^#, LI Song^*

National Engineering Research Center for the Strategic Drug of AMMS, Beijing 100850, China

Received:2024-05-27 Online:2024-07-15 Published:2024-07-31

摘要/Abstract

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。

关键词: 抗体偶联药物, 抗肿瘤, 效应分子, 毒性, 安全性

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.

Key words: antibody drug conjugate, antitumor, payloads, toxicity, safety

中图分类号:

R979.1

刘连奇, 肖典, 钟武, 周辛波, 李松. 抗体偶联药物的相关毒性和研究对策[J]. 中国药物警戒, 2024, 21(7): 721-729.

LIU Lianqi, XIAO Dian, ZHONG Wu, ZHOU Xinbo, LI Song. Toxicity associated with antibody-drug conjugates and corresponding research strategies[J]. Chinese Journal of Pharmacovigilance, 2024, 21(7): 721-729.

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抗体偶联药物的相关毒性和研究对策

Toxicity associated with antibody-drug conjugates and corresponding research strategies

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