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.

双特异性抗体的研究在过去二十年中取得了巨大进展，双特异性抗体旨在同时结合两种抗原或表位。由于蛋白质工程技术的进步和大量的临床前研究工作，双特异性抗体正在不断开发和优化，以提高其功效并减轻毒性。迄今为止，这些药物中有 >200 正在进行临床前或临床评估，其中大多数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。我们还讨论了新型替代双特异性抗体构建体，例如针对肿瘤细胞或位于肿瘤微环境中的细胞表达的两种抗原的抗体构建体。最后，我们考虑了这个快速发展领域的未来研究方向，包括创新的抗体工程策略，这可能会实现更有效的递送，克服耐药性，从而优化临床结果。