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Review
. 2023 Sep;13(9):3583-3597.
doi: 10.1016/j.apsb.2023.05.023. Epub 2023 May 23.

Bispecific antibodies in cancer therapy: Target selection and regulatory requirements

Yanze Sun  1   2   3 , Xinmiao Yu  1   2   3 , Xiao Wang  1   2   3 , Kai Yuan  1   2   3 , Gefei Wang  1   2   3 , Lingrong Hu  1   2   3 , Guoyu Zhang  1   2   3 , Wenli Pei  1   2   3 , Liping Wang  1   2   3 , Chengliang Sun  1   2   3 , Peng Yang  1   2   3
Affiliations
Review

Bispecific antibodies in cancer therapy: Target selection and regulatory requirements

Yanze Sun et al. Acta Pharm Sin B. 2023 Sep.

Abstract

In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.

Keywords: Bispecific antibody; Cancer immunotherapy; Clinical trials; Mechanism; Oncology; Regulatory guidance; Structure; Target selection.

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Figures

Image 1
Graphical abstract
Figure 1
Figure 1
Preferred targets and combinations. (A) The top 10 most widely investigated targets. (B) The top 10 most widely investigated targets–clinical stage. (C) Top 10 selected target combinations of cell-bridging bsAbs and (D) their clinical phases. (E) Top 10 selected target combinations of non-cell-bridging bsAbs and (F) their clinical phases. Information was obtained from Cortellis Drug Discovery Intelligence (https://www.cortellis.com/drugdiscovery/home).
Figure 2
Figure 2
Representative bispecific antibodies and their format. According to the existence of the Fc region, bispecific antibodies can be divided into two categories: (A) IgG-based bsAbs and (B) Fragment-based bsAbs. BiTE, bispecific T-cell engager; TandAb, tandem diabody; DART, dual affinity retargeting.
Figure 3
Figure 3
Bispecific antibodies in cancer therapy would be classified into four categories based on mechanism and target selection. (A) BsAbs that bridge immune effector cells to tumor cells, including pan T cells, γδ T cells and NK (natural killer) cells, etc. (B) BsAbs that bridge receptors from the same or different cells. (C) BsAbs that bridge cytokines and receptors. (D) BsAbs that bridge two cytokines.
Figure 4
Figure 4
Representative bispecific antibodies with increased efficacy and reduced toxicity based on their unique structures.
Figure 5
Figure 5
Representative innovative bispecific antibody drugs. (A) ZW49 is a bispecific ADC. (B) SAR-442257 is a trispecific antibody. (C) GNC-038 is a tetraspecific antibody (ClinicalTrials.gov identifier: NCT05192486).
See this image and copyright information in PMC

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