SCI
1 July 2024
Bispecific and multispecific antibodies in oncology: opportunities and challenges
(Nature Reviews Clinical Oncology, IF: 81.1)
Maria-Elisabeth Goebeler, Gernot Stuhler & Ralf Bargou
CORRESPONDENCE TO: Goebeler_m@ukw.de
Research into bispecific antibodies, which are designed to simultaneously bind two antigens or epitopes, has advanced enormously over the past two decades. Owing to advances in protein engineering technologies and considerable preclinical research efforts, bispecific antibodies are constantly being developed and optimized to improve their efficacy and to mitigate toxicity. To date, >200 of these agents, the majority of which are bispecific immune cell engagers, are in either preclinical or clinical evaluation. In this Review, we discuss the role of bispecific antibodies in patients with cancer, including history and development, as well as innovative targeting strategies, clinical applications, and adverse events. We also discuss novel alternative bispecific antibody constructs, such as those targeting two antigens expressed by tumour cells or cells located in the tumour microenvironment. Finally, we consider future research directions in this rapidly evolving field, including innovative antibody engineering strategies, which might enable more effective delivery, overcome resistance, and thus optimize clinical outcomes.
在过去的二十年里,设计用于同时结合两种抗原或表位的双特异性抗体的研究取得了巨大进展。由于蛋白质工程技术的进步和大量的临床前研究工作,双特异性抗体正得到不断开发和优化,以提高其疗效并减轻毒性。到目前为止,这类药物中有200多种正在进行临床前或临床评估,其中大多数这类药物是双特异性免疫细胞接合剂。在这篇综述中,我们讨论了双特异性抗体在癌症患者中的作用,包括其历史和发展,以及创新的靶向策略、临床应用和不良事件。我们还讨论了新的替代双特异性抗体构建体,例如那些靶向肿瘤细胞或肿瘤微环境中的由细胞表达的两种抗原的构建体。最后,我们考虑了这一快速发展领域的未来研究方向,包括抗体工程创新策略,这会使递送更有效,克服耐药性,进而优化临床结果。