Xu Guanghui, Luo Yuting, Wang Hanbing, Wang Yue, Liu Baorui, Wei Jia
The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, China.
The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, China; Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, 210008, China.
Cancer Lett. 2022 Jul 10;538:215699. doi: 10.1016/j.canlet.2022.215699. Epub 2022 Apr 27.
Bispecific antibodies (BsAbs)-based therapeutics have been identified to be one of the most promising immunotherapy strategies. However, their target repertoire is mainly restricted to cell surface antigens rather than intracellular antigens, resulting in a relatively limited scope of applications. Intracellular tumor antigens are identified to account for a large proportion of tumor antigen profiles. Recently, bsAbs that target intracellular oncoproteins have raised much attention, broadening the targeting scope of tumor antigens and improving the efficacy of traditional antibody-based therapeutics. Consequently, this review will focus on this emerging field and discuss related research advances. We introduce the classification, characteristics, and clinical applications of bsAbs, the theoretical basis for targeting intracellular antigens, delivery systems of bsAbs, and the latest preclinical and clinical advances of bsAbs targeting several intracellular oncotargets, including those of cancer-testis antigens, differentiation antigens, neoantigens, and other antigens. Moreover, we summarize the limitations of current bsAbs, and propose several potential strategies against immune escape and T cell exhaustion as well as some future perspectives.
基于双特异性抗体（BsAbs）的疗法已被确定为最有前途的免疫治疗策略之一。然而，它们的靶点主要局限于细胞表面抗原而非细胞内抗原，导致应用范围相对有限。细胞内肿瘤抗原在肿瘤抗原谱中占很大比例。最近，靶向细胞内癌蛋白的双特异性抗体引起了广泛关注，拓宽了肿瘤抗原的靶向范围，提高了传统抗体疗法的疗效。因此，本综述将聚焦于这一新兴领域，并讨论相关研究进展。我们介绍了双特异性抗体的分类、特点和临床应用、靶向细胞内抗原的理论基础、双特异性抗体的递送系统，以及靶向几种细胞内肿瘤靶点（包括癌-睾丸抗原、分化抗原、新抗原和其他抗原）的双特异性抗体的最新临床前和临床进展。此外，我们总结了当前双特异性抗体的局限性，并提出了几种对抗免疫逃逸和T细胞耗竭的潜在策略以及一些未来展望。
