Prodrug-based bispecific antibodies for cancer therapy: advances and future directions

作者：Zhengdong Ai, Bing Wang, Yunlong Song, Panpan Cheng, Xinlin Liu, Peng Sun · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1523693 · 被引用次数：24 · 研究领域：Monoclonal and Polyclonal Antibodies Research、Glycosylation and Glycoproteins Research、Advanced Biosensing Techniques and Applications

Bispecific antibodies represent an innovative paradigm in cancer therapy, offering broader therapeutic potential compared to conventional monoclonal antibodies. To increase tumor selectivity while mitigating off-target effects in normal tissues, the concept of prodrug-based bispecific antibodies has emerged. This review delineates the various mechanisms underlying the action of prodrug-based bispecific antibodies, including protease-mediated activation, steric hindrance release via proteolytic processing, activation by soluble factors, conditional assembly, and chain exchange-mediated activation. We also address the critical challenges that must be overcome to optimize the development and clinical application of these sophisticated therapeutic agents.