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《工程(英文)》 >> 2021年 第7卷 第11期 doi: 10.1016/j.eng.2020.06.030

提升疗效的修饰型治疗性抗体国内外研究进展

a Department of Cell Biology, National Translational Science Center for Molecular Medicine, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, Xi'an 710032, China
b Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
c Department of Hepatobiliary Surgery, Air Force Medical Center, Beijing 100142, China

收稿日期: 2019-09-29 修回日期: 2020-04-14 录用日期: 2020-06-24 发布日期: 2021-07-28

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摘要

生物治疗药物市场的繁荣反映了治疗性抗体药物用于治疗癌症、炎性疾病和难治性感染的可行性和有效性。随着抗体药物临床试验和转化研究中出现的结合效率不高、效应功能降低和不良反应频发等问题的解决,治疗性抗体的修饰在抗体药物的研发进程中得到了前所未有的蓬勃发展。为了提升抗体的结合活性、循环中的半衰期、靶细胞的有效性,并最终实现改善抗体药物的疗效,抗体可主要通过以下途径修饰:①糖基化修饰;②抗体恒定区(Fc)改造;③抗体亚类重构;④构建抗体-药物偶联物(ADC);⑤基于单链可变区片段(scFv)的嵌合抗原受体T细胞(CAR-T);⑥双特异性抗体(bsAb)。过去几十年来全球在修饰型治疗性抗体的领域取得了许多成就,中国作为对于生物治疗药物需求巨大并且拥有巨大研发潜力的国家在该领域亦发挥了积极作用。本文概括了修饰型治疗性抗体在当前国际研究中取得的进展,并在单独的章节中重点介绍了中国在该领域取得的成果。

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