Application and future prospects of bispecific antibodies in the treatment of non-small cell lung cancer

As the leading cause of cancer-related deaths, lung cancer remains a noteworthy threat to human health. Although immunotherapies, such as immune checkpoint inhibitors (ICIs), have significantly increased the efficacy of lung cancer treatment, a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance. Bispecific antibodies (bsAbs) bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles, thus attracting increasing attention as novel antitumor therapies. At present, in addition to the approved bsAb, amivantamab, three novel bsAbs (KN046, AK112, and SHR-1701) are being evaluated in phase 3 clinical trials and many bsAbs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer (NSCLC). Herein we present the structure, classification, and mechanism of action underlying bsAbs in NSCLC and introduce related clinical trials. Finally, we discuss challenges, potential solutions, and future prospects in the context of cancer treatment with bsAbs.