Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Trends Cancer. 2024 Oct;10(10):893-919. doi: 10.1016/j.trecan.2024.07.002. Epub 2024 Aug 30.
Bispecific antibodies (bsAbs) are engineered molecules designed to target two different epitopes or antigens. The mechanism of action is determined by the bsAb molecular targets and structure (or format), which can be manipulated to create variable and novel functionalities, including linking immune cells with tumor cells, or dual signaling pathway blockade. Several bsAbs have already changed the treatment landscape of hematological malignancies and select solid cancers. However, the mechanisms of resistance to these agents are understudied and the management of toxicities remains challenging. Herein, we review the principles in bsAb engineering, current understanding of mechanisms of action and resistance, data for clinical application, and provide a perspective on ongoing challenges and future developments in this field.
双特异性抗体(bsAbs)是经过设计的工程化分子,旨在靶向两个不同的表位或抗原。作用机制取决于 bsAb 的分子靶标和结构(或形式),可以对其进行操纵以产生可变的新颖功能,包括将免疫细胞与肿瘤细胞连接,或双重信号通路阻断。几种 bsAbs 已经改变了血液系统恶性肿瘤和部分实体瘤的治疗格局。然而,这些药物的耐药机制仍研究不足,毒性管理仍然具有挑战性。本文综述了 bsAb 工程的原理、目前对作用机制和耐药机制的认识、临床应用数据,并对该领域当前的挑战和未来的发展提供了展望。