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

Bispecific Antibodies: From Research to Clinical Application

Jiabing Ma  1 , Yicheng Mo  1 , Menglin Tang  2 , Junjie Shen  3 , Yanan Qi  2 , Wenxu Zhao  2 , Yi Huang  3 , Yanmin Xu  2 , Cheng Qian  4
Affiliations

Bispecific Antibodies: From Research to Clinical Application

Jiabing Ma et al. Front Immunol. .

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.

Keywords: BsAbs; application; development; mechanism; platform.

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Conflict of interest statement

Authors JS and YH were employed by the company Chongqing Precision Biotech Co., Ltd. Authors YQ, WZ, MT, and YX were employed by the company Chongqing Institute of Precision Medicine and Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Classical molecular platform of BsAbs and representative antibodies.
Figure 2
Figure 2
Some classic structures of BsAbs with CD3 as one of their targets.
Figure 3
Figure 3
Mechanisms and clinical study of three market BsAbs: (A) Catumaxomab (B) Blinatumomab (C) Emicizumab (D) phase of three market BsAbs (E) status of three market BsAbs.
See this image and copyright information in PMC

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