B7-H3 as a promising target for cytotoxicity T cell in human cancer therapy
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Juan Ma1,*, Pan Ma2,*, Chenghai Zhao3,*, Xin Xue4, Huamin Han5, Changzhen Liu6, Hua Tao5, Weigang Xiu1, Jia Cai1, Man Zhang1,7
1Department of Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China
2Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
3Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China
4Department of Immunology, China Basic Medical Theory of Chinese Medicine, Academy of Chinese Medical Sciences, Beijing, China
5CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
6Department of Molecular Biology, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
7Chinese Medical Doctor Association of Lab Medicine, Beijing, China
*These authors have contributed equally to this work
Juan Ma, e-mail: [email protected]
Man Zhang, e-mail: [email protected]
Keywords: B7-H3, bispecific antibody, immunotherapy
Received: September 24, 2015 Accepted: March 28, 2016 Published: April 18, 2016
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.
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