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

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...

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Bibliographic Details
Main Authors: Zhijuan Ai, Bing Wang, Yunlong Song, Panpan Cheng, Xinlin Liu, Peng Sun
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1523693/full
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Summary: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.
ISSN:1664-3224