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

被引：55
作者：
Yang, Shuo [1 ,2 ]
Cao, Bihui [3 ,4 ]
Zhou, Guangyu [1 ,2 ]
Zhu, Lipeng [1 ,2 ]
Wang, Lu [3 ,4 ]
Zhang, Li [5 ]
Kwok, Hang Fai [1 ,2 ]
Zhang, Zhenfeng [3 ,4 ]
Zhao, Qi [1 ,2 ]
机构：
[1] Univ Macau, Canc Ctr, Fac Hlth Sci, Taipa, Macao, Peoples R China
[2] Univ Macau, Inst Translat Med, Fac Hlth Sci, Taipa, Macao, Peoples R China
[3] Guangzhou Med Univ, Affiliated Hosp 2, Key Lab Nanoimmunoregulat Tumor Microenviroment, Dept Radiol,Translat Med Ctr, Guangzhou, Peoples R China
[4] Guangzhou Med Univ, Affiliated Hosp 2, Key Lab Nanoimmunoregulat Tumor Microenviroment, Guangdong Prov Educ Dept, Guangzhou, Peoples R China
[5] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA
来源：
FRONTIERS IN PHARMACOLOGY | 2020年 / 11卷
基金：
国家重点研发计划;
关键词：
B7-H3; chimeric antigen receptor; NK-92; immune checkpoint; natural killer cell; CAR-T; EXPRESSION; TUMORS; CD276; NK-92;
D O I：
10.3389/fphar.2020.01089
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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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页数：10
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