Narrative review of research progress and future development of bispecific antibodies in lung cancer: opportunities and challenges.

BACKGROUND AND OBJECTIVE: Lung cancer remains a leading cause of cancer-related mortality worldwide. Despite the advances being achieved in the development of targeted therapies and immune checkpoint inhibitors (ICIs), tumor heterogeneity, acquired resistance, and the scarcity of effective salvage regimens continue to limit positive long-term outcomes. In recent years, bispecific antibodies (BsAbs) have garnered substantial attention as a promising modality for address these unmet needs. This review was conducted to characterize the research on BsAbs in lung cancer therapy, with a focus on their mechanisms of action, clinical development, current challenges, and future directions. METHODS: A comprehensive literature search for clinical studies and reviews published in English from January 1, 2020 to May 1, 2026, was conducted in the PubMed, Web of Science, and ClinicalTrials.gov databases with keywords such as "bispecific antibodies" and "lung cancer". KEY CONTENT AND FINDINGS: BsAbs concurrently engage two distinct antigens to redirect immune effector cells or inhibit multiple oncogenic signaling pathways via four primary mechanisms: immune bridging, receptor blockade, immune checkpoint targeting, and bispecific antibody-drug conjugates (BsADCs). Recent years landmark trials have cemented the role of BsAbs in lung cancer such as MARIPOSA (amivantamab), HARMONi-A (ivonescimab) and DeLLphi-304 (tarlatamab), and more dual/multi-specific antibodies with new targets and new mechanisms of action have entered the clinical stage. However, how to reduce toxicity and enhance efficacy, as well as optimize the combined treatment strategies, still remains a major challenge in the future development of dual/multi-specific antibodies. CONCLUSIONS: BsAbs represent a promising therapeutic strategy for lung cancer. Continued advances in antibody engineering, target identification, and clinical application strategies are expected to further improve their therapeutic potential and expand their role in the treatment of lung cancer.