Abstract:
Bispecific antibodies (bsAbs) are a class of engineered antibodies capable of simultaneously recognizing and binding to two distinct antigens or two different epitopes of the same antigen. In recent years, they have demonstrated remarkable therapeutic potential in malignant tumors, autoimmune diseases, and other fields. This review systematically summarizes the developmental trajectory and structural classifications of bsAbs, with a particular focus on three principal mechanisms of action: immune cell redirection, synergistic regulation of signaling pathways, and targeted delivery of effector molecules. The design features and engineering optimization strategies of IgG-like and non-IgG-like formats are also discussed. Clinically, bsAbs have achieved breakthrough progress in hematologic malignancies and are gradually expanding into solid tumors and autoimmune diseases. Representative drugs such as Blinatumomab, Teclistamab, and Cadonilimab have already reached market approval. Addressing the safety concerns of bsAbs, as well as challenges including short half-life, immune evasion, and limited tumor penetration, recent research has focused on strategies such as logic-gated design, prodrug antibodies, mRNA delivery platforms, and trispecific formats to enhance therapeutic selectivity and functional diversity. With continuous advances in antibody engineering, delivery systems, and combination therapies, bsAbs are expected to become a cornerstone of precision immunotherapy, offering more effective and safer treatment options for complex diseases.