B7-H3 as a promising target for cytotoxicity T cell in human cancer therapy

// Juan Ma 1, * , Pan Ma 2, * , Chenghai Zhao 3, * , Xin Xue 4 , Huamin Han 5 , Changzhen Liu 6 , Hua Tao 5 , Weigang Xiu 1 , Jia Cai 1 , Man Zhang 1 , 7 1 Department of Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China 2 Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China 3 Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China 4 Department of Immunology, China Basic Medical Theory of Chinese Medicine, Academy of Chinese Medical Sciences, Beijing, China 5 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China 6 Department of Molecular Biology, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China 7 Chinese Medical Doctor Association of Lab Medicine, Beijing, China * These authors have contributed equally to this work Correspondence to: Juan Ma, e-mail: atiger10@163.com Man Zhang, e-mail: MZhang99@aliyun.com Keywords: B7-H3, bispecific antibody, immunotherapy Received: September 24, 2015      Accepted: March 28, 2016      Published: April 18, 2016 ABSTRACT Targeting B7-H3 over-expressed tumor cells with anti-B7-H3 monoclonal antibodies inhibits tumor growth. Here we demonstrated the expression of B7 family homologue 3 (B7-H3) in a wide range of human tumor cells and further investigated whether B7-H3 could be served as a target for T-cell mediated immunotherapy against human cancers. The specific cytotoxic activity of activated T cell (ATC) armed with a novel anti-CD3 x anti-B7-H3 bispecific antibody (B7-H3Bi-Ab) against tumor cell was evaluated in vitro and in vivo. In contrast with unarmed ATC, an increase in cytotoxic activity of B7-H3Bi-armed ATC against tumor cells was observed at effector/target (E/T) ratios of 5:1, 10:1, and 20:1. Moreover, B7-H3Bi-armed ATC secreted more IFN-γ, TNF-α and IL-2 than unarmed ATC. Infusion of B7-H3Bi-armed ATC inhibited tumor growth in severe combined immunodeficiency (SCID) xenograft models, along with a significant survival benefit. Therefore, treatment with novel B7-H3Bi-armed ATC will be a promising strategy for current cancer immunotherapy.