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Challenges and strategies for next-generation bispecific antibody-based antitumor therapeutics

Cellular & Molecular Immunology volume 17, pages 451–461 (2020)Cite this article

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Abstract

Bispecific antibodies (bsAbs) refer to a large family of molecules that recognize two different epitopes or antigens. Although a series of challenges, especially immunogenicity and chain mispairing issues, once hindered the development of bsAbs, they have been gradually overcome with the help of rapidly developing technologies in the past 5 decades. In the meantime, an increasing number of bsAb platforms have been designed to satisfy different clinical demands. Currently, numerous preclinical and clinical trials are underway, portraying a promising future for bsAb-based cancer treatment. Nevertheless, bsAb drugs still face enormous challenges in their application as cancer therapeutics, including tumor heterogeneity and mutational burden, intractable tumor microenvironment (TME), insufficient costimulatory signals to activate T cells, the necessity for continuous injection, fatal systemic side effects, and off-target toxicities to adjacent normal cells. Therefore, we provide several strategies as solutions to these issues, which comprise generating multispecific bsAbs, discovering neoantigens, combining bsAbs with other anticancer therapies, exploiting natural killer (NK)-cell-based bsAbs and producing bsAbs in situ. In this review, we mainly discuss previous and current challenges in bsAb development and underscore corresponding strategies, with a brief introduction of several typical bsAb formats.

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Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China

    Heliang Li, Phei Er Saw & Erwei Song

  2. Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China

    Heliang Li & Erwei Song

  3. Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou, 510080, China

    Erwei Song

  4. Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510005, China

    Erwei Song

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  1. Heliang Li
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  2. Phei Er Saw
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  3. Erwei Song
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Correspondence to Erwei Song.

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Li, H., Er Saw, P. & Song, E. Challenges and strategies for next-generation bispecific antibody-based antitumor therapeutics. Cell Mol Immunol 17, 451–461 (2020). https://doi.org/10.1038/s41423-020-0417-8

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  • DOI: https://doi.org/10.1038/s41423-020-0417-8

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