Advances in the clinical application of bispecific antibodies in cancer therapy

Shiqi Zhou; Feng Li; Mengke Niu; Kongming Wu; Tianye Li; Ming Yi

doi:10.1016/j.isci.2025.114203

Advances in the clinical application of bispecific antibodies in cancer therapy

iScience. 2025 Nov 25;28(12):114203. doi: 10.1016/j.isci.2025.114203. eCollection 2025 Dec 19.

Authors

Shiqi Zhou^{1

2}, Feng Li³, Mengke Niu⁴, Kongming Wu⁵, Tianye Li¹, Ming Yi⁴

Affiliations

¹ Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
² Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
³ Department of Pulmonary Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
⁴ Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
⁵ Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Shanxi, China.

Abstract

Cancer immunotherapy has emerged as one of the most groundbreaking advancements. However, the tumor microenvironment (TME) is often dominated by various immunosuppressive factors, compromising the efficacy of single-target therapies, leading to non-responsiveness or resistance. Bispecific antibodies (BsAbs) represent an innovative immunotherapeutic strategy with enormous potential for improving cancer treatment outcomes. Unlike monoclonal antibodies, BsAbs can concurrently inhibit multiple pro-tumor pathways, target immune checkpoints to mitigate resistance, and bind to two distinct antigens, thereby enhancing specificity while minimizing off-target effects. Moreover, BsAbs are more cost-efficient and less toxic compared to the use of two separate monoclonal antibodies in combination. In recent decades, BsAbs have made remarkable progress in clinical development. Several BsAbs, such as blinatumomab, mosunetuzumab, teclistamab, glofitamab, epcoritamab, talquetamab, ivonescimab, cadonilimab, tarlatamab, zenocutuzumab, and catumaxomab, have achieved notable success in clinical trials. This review highlights clinically approved BsAbs and provides a comprehensive summary of their therapeutic applications in cancer treatment.

Keywords: Cellular therapy; Oncology; Therapeutics.

Publication types

Review