双特异性抗体 (bsAb) 是设计用于靶向两个不同表位或抗原的工程分子。作用机制由 bsAb 分子靶点和结构（或形式）决定，可对其进行操作以创建可变的新颖功能，包括将免疫细胞与肿瘤细胞连接或双重信号通路阻断。几种双特异性抗体已经改变了血液恶性肿瘤和特定实体癌的治疗格局。然而，对这些药物的耐药机制尚未得到充分研究，毒性的管理仍然具有挑战性。在此，我们回顾了双特异性抗体工程的原理、目前对作用和耐药机制的理解、临床应用数据，并提供了对该领域持续挑战和未来发展的看法。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

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.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.