Journal
ONCOTARGET
Volume 7, Issue 20, Pages 29480-29491Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8784
Keywords
B7-H3; bispecific antibody; immunotherapy
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Funding
- National Nature Science Foundation of China [31400754]
- Ministry of Science and Technology of China (S & T major Program) [2012ZX1004701-001-002]
- Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics [Z151100001615060]
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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-gamma, TNF-alpha 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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