B7-H3 as a promising target for cytotoxicity T cell in human cancer therapy.
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.
Department of Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China.
Juan
J
Ma
Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Pan
P
Ma
Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China.
Chenghai
C
Zhao
Department of Immunology, China Basic Medical Theory of Chinese Medicine, Academy of Chinese Medical Sciences, Beijing, China.
Xin
X
Xue
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Huamin
H
Han
Department of Molecular Biology, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China.
Changzhen
C
Liu
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Hua
H
Tao
Department of Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China.
Weigang
W
Xiu
Department of Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China.
Jia
J
Cai
Department of Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China.|Chinese Medical Doctor Association of Lab Medicine, Beijing, China.
Man
M
Zhang
D000818:Animals; D018033:Antibodies, Bispecific / Q000494:pharmacology*; D060887:B7 Antigens / Q000037:antagonists & inhibitors* / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
D018033:Antibodies, Bispecific; D060887:B7 Antigens; C423237:CD276 protein, human
B7-H3; bispecific antibody; immunotherapy