双特异性抗体
免疫原性
计算机科学
癌症
抗原
肿瘤微环境
计算生物学
医学
癌症研究
抗体
免疫学
肿瘤细胞
单克隆抗体
生物
内科学
作者
Heliang Li,Phei Er Saw,Erwei Song
标识
DOI:10.1038/s41423-020-0417-8
摘要
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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