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

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.

journal_name

Cell Mol Immunol

journal_title

Cellular & molecular immunology

authors

Li H,Er Saw P,Song E

doi

10.1038/s41423-020-0417-8

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

451-461

issue

5

eissn

1672-7681

issn

2042-0226

pii

10.1038/s41423-020-0417-8

journal_volume

17

pub_type

杂志文章,评审

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