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《工程(英文)》 >> 2021年 第7卷 第11期 doi: 10.1016/j.eng.2020.10.024

一种通过计算机辅助抗体设计技术获得的靶向人表皮生长因子受体2的新型全人抗体HF

a State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Beijing 100850, China

b Beijing Key Laboratory of Therapeutic Gene Engineering Antibody, Beijing 100850, China

c Institute of Military Cognitive and Brain Sciences, Beijing 100850, China

d Beijing Mabworks Biotech Co. Ltd., Beijing 100176, China

e Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China

# These authors contributed equally to this work.

收稿日期: 2019-09-03 修回日期: 2020-07-30 录用日期: 2020-10-18 发布日期: 2021-09-30

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摘要

全人抗体免疫原性小、安全性高。目前研究的处于临床试验阶段的大多数抗体药物都是人源化或全人抗体。全人抗体多通过噬菌体展示技术(体外)或转基因小鼠(体内)产生;其他方法包括B淋巴细胞永生化、人-人杂交瘤、单细胞聚合酶链反应等。本文描述了一种基于分子结构的计算机辅助设计新抗体技术,用于获得全人抗体。由于靶向人表皮生长因子受体2(HER2)的注射用曲妥珠单抗(赫赛汀)的结构复杂,我们首先针对赫赛汀识别HER2 的潜在表位设计了6 条短肽。随后,将这些肽作为抗体互补决定区,并采用适合的免疫球蛋白框架,获得名为“HF”的新型抗HER2 抗体。HF比赫赛汀具有更高的亲和力和更有效的抗肿瘤活性。我们的工作为用于机理研究以及免疫相关疾病(如癌症和传染病)的成像和临床应用的新型全人抗体的快速设计和筛选提供了有用工具。

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