Targeting B7-H3 Immune Checkpoint With Chimeric Antigen Receptor-Engineered Natural Killer Cells Exhibits Potent Cytotoxicity Against Non-Small Cell Lung Cancer

Chimeric antigen receptor (CAR)-modified natural killer (NK) cell therapy represents a kind of promising anti-cancer treatment because CAR renders NK cells activation and recognition specificity toward tumor cells. An immune checkpoint molecule, B7-H3, plays an inhibitory role in modulation of NK ce...

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Published inFrontiers in pharmacology Vol. 11; p. 1089
Main Authors Yang, Shuo, Cao, Bihui, Zhou, Guangyu, Zhu, Lipeng, Wang, Lu, Zhang, Li, Kwok, Hang Fai, Zhang, Zhenfeng, Zhao, Qi
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 30.07.2020
Subjects
B7-H3
chimeric antigen receptor
immune checkpoint
natural killer cell
NK-92
Pharmacology
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Summary:Chimeric antigen receptor (CAR)-modified natural killer (NK) cell therapy represents a kind of promising anti-cancer treatment because CAR renders NK cells activation and recognition specificity toward tumor cells. An immune checkpoint molecule, B7-H3, plays an inhibitory role in modulation of NK cells. To enhance NK cell functions, we generated NK-92MI cells carrying anti-B7-H3 CAR by lentiviral transduction. The expression of anti-B7-H3 CAR significantly enhanced the cytotoxicity of NK-92MI cells against B7-H3-positive tumor cells. In accordance with enhanced cytotoxicity, the secretions of perforin/granzyme B and expression of CD107a were highly elevated in anti-B7-H3 CAR-NK-92MI cells. Moreover, compared to unmodified NK-92MI cells, anti-B7-H3 CAR-NK-92MI cells effectively limited tumor growth in mouse xenografts of non-small cell lung cancer and significantly prolonged the survival days of mice. This study provides the rationale and feasibility of B7-H3-specific CAR-NK cells for application in adoptive cancer immunotherapy.
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Reviewed by: Xiuli Wu, Jinan University, China; Wei Li, University of Pittsburgh, United States
This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology
Edited by: Dong-Hua Yang, St. John’s University, United States
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2020.01089