Research Progress and Clinical Applications of Bispecific Antibodies

Bispecific antibodies (bsAbs) are a class of engineered antibodies capable of simultaneously recognizing two distinct antigenic epitopes. In recent years, they have demonstrated significant therapeutic potential in the treatment of malignant tumors, autoimmune diseases, and other conditions. This review provides a comprehensive overview of the development and structural classification of bsAbs, with a focus on three primary mechanisms of action: immune cell redirection, synergistic modulation of signaling pathways, and targeted delivery of effector molecules. The structural features and engineering strategies of both IgG-like and non-IgG-like formats are summarized. Clinically, bsAbs have achieved notable breakthroughs in hematologic malignancies and are being increasingly applied to solid tumors and autoimmune disorders. Representative drugs such as Blinatumomab, Teclistamab, and Cadonilimab have already gained regulatory approval. To overcome challenges such as safety concerns, short half-life, immune evasion, and poor tumor penetration, recent studies have focused on logic-gated designs, antibody prodrugs, mRNA delivery platforms, and trispecific constructs to enhance therapeutic selectivity and functional diversity. With continuous advances in antibody engineering, delivery technologies, and combination treatment strategies, bsAbs are poised to become a cornerstone of precision immunotherapy, offering safer and more effective solutions for complex diseases.