Zhiyu Liu, Yang Zhang, Man Xue, Zhaoxia Wang
Acquired resistance and the immunosuppressive microenvironment remain major challenges in the treatment of advanced lung cancer. By leveraging dual-target synergy, bispecific antibodies (BsAbs) mediate multiple functions, including immune cell engagement, immune checkpoint blockade, and signaling pathway inhibition. These properties offer novel strategies to overcome existing therapeutic limitations. This review comprehensively describes the structural features and core mechanisms of action of BsAbs, reviews their key clinical advances in lung cancer, and analyzes ongoing clinical challenges, such as resistance, mechanism-based toxicities, and biomarker identification. Furthermore, it discusses future directions in structural optimization and combination therapy to provide insights for precision oncology in lung cancer.