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双特异性抗体:从研究到临床应用。

Bispecific Antibodies: From Research to Clinical Application.

机构信息

College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.

IND Center, Chongqing Institute of Precision Medicine and Biotechnology Co., Ltd., Chongqing, China.

出版信息

Front Immunol. 2021 May 5;12:626616. doi: 10.3389/fimmu.2021.626616. eCollection 2021.

DOI:10.3389/fimmu.2021.626616
PMID:34025638
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8131538/
Abstract

Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical therapeutic effects of BsAbs are superior to those of monoclonal antibodies (MoAbs), with broad applications for tumor immunotherapy as well as for the treatment of other diseases. Recently, with progress in antibody or protein engineering and recombinant DNA technology, various platforms for generating different types of BsAbs based on novel strategies, for various uses, have been established. More than 30 mature commercial technology platforms have been used to create and develop BsAbs based on the heterologous recombination of heavy chains and matching of light chains. The detailed mechanisms of clinical/therapeutic action have been demonstrated with these different types of BsAbs. Three kinds of BsAbs have received market approval, and more than 110 types of BsAbs are at various stages of clinical trials. In this paper, we elaborate on the classic platforms, mechanisms, and applications of BsAbs. We hope that this review can stimulate new ideas for the development of BsAbs and improve current clinical strategies.

摘要

双特异性抗体(BsAbs)是指具有两个结合位点的抗体,分别针对两个不同的抗原或同一抗原上的两个不同表位。BsAbs 的临床治疗效果优于单克隆抗体(MoAbs),在肿瘤免疫治疗以及治疗其他疾病方面具有广泛的应用。近年来,随着抗体或蛋白质工程以及重组 DNA 技术的进步,基于新型策略的不同类型的 BsAbs 的各种生成平台已经建立,用于各种用途。超过 30 种成熟的商业技术平台已被用于基于重链的异源重组和轻链的匹配来创建和开发 BsAbs。这些不同类型的 BsAbs 的详细临床/治疗作用机制已经得到了证明。已有三种 BsAbs 获得市场批准,超过 110 种 BsAbs 处于不同的临床试验阶段。本文详细阐述了 BsAbs 的经典平台、机制和应用。我们希望这篇综述能为 BsAbs 的开发激发新的思路,并改进当前的临床策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f9/8131538/d367afc9d5a1/fimmu-12-626616-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f9/8131538/381b602459a7/fimmu-12-626616-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f9/8131538/15a1ee0242c8/fimmu-12-626616-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f9/8131538/d367afc9d5a1/fimmu-12-626616-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f9/8131538/381b602459a7/fimmu-12-626616-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f9/8131538/15a1ee0242c8/fimmu-12-626616-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f9/8131538/d367afc9d5a1/fimmu-12-626616-g003.jpg

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