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.

引用

页数：10

共 44 条

[21] The pronounced cytotoxic effects of chimeric antigen receptor T cells targeting B7-H3 in organoids and liver xenografts derived from colorectal cancer patients [J].

Sheng, Yuling ;

Yan, Li ;

Liu, Qi ;

Peng, Yifan ;

Tan, Jingyun ;

Li, Wenhua ;

Mao, Wei ;

Wei, Wenqing ;

Chang, Yanyun ;

Cao, Linlin ;

Tan, Yi ;

Xiao, Yanlin ;

Zhang, Wenyong ;

Gao, Jing ;

Xu, Yang ;

Du, Changzheng .

BRITISH JOURNAL OF CANCER, 2025,

[22] EPHA5 mutation impairs natural killer cell-mediated cytotoxicity against non-small lung cancer cells and promotes cancer cell migration and invasion [J].

Zhang, Jingwen ;

Zhang, Zhihao ;

Song, Weiwei ;

Liu, Jumin .

MOLECULAR AND CELLULAR PROBES, 2020, 52

[23] CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors [J].

Majzner, Robbie G. ;

Theruvath, Johanna L. ;

Nellan, Anandani ;

Heitzeneder, Sabine ;

Cui, Yongzhi ;

Mount, Christopher W. ;

Rietberg, Skyler P. ;

Linde, Miles H. ;

Xu, Peng ;

Rota, Christopher ;

Sotillo, Elena ;

Labanieh, Louai ;

Lee, Daniel W. ;

Orentas, Rimas J. ;

Dimitrov, Dimiter S. ;

Zhu, Zhongyu ;

St Croix, Brad ;

Delaidelli, Alberto ;

Sekunova, Alla ;

Bonvini, Ezio ;

Mitra, Siddhartha S. ;

Quezado, Martha M. ;

Majeti, Ravindra ;

Monje, Michelle ;

Sorensen, Poul H. B. ;

Maris, John M. ;

Mackall, Crystal L. .

CLINICAL CANCER RESEARCH, 2019, 25 (08) :2560-2574

[24] Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer [J].

Feng, Kaichao ;

Guo, Yelei ;

Dai, Hanren ;

Wang, Yao ;

Li, Xiang ;

Jia, Hejin ;

Han, Weidong .

SCIENCE CHINA-LIFE SCIENCES, 2016, 59 (05) :468-479

[25] RETRACTED: Clinical significance of the induction of macrophage differentiation by the costimulatory molecule B7-H3 in human non-small cell lung cancer (Retracted Article) [J].

Sun, Jing ;

Mao, Yong ;

Zhang, Yang-Qin ;

Guo, Yun-Di ;

Mu, Chuan-Yong ;

Fu, Feng-Qing ;

Zhang, Xue-Guang .

ONCOLOGY LETTERS, 2013, 6 (05) :1253-1260

[26] Chimeric antigen receptor-T cells are effective against CEACAM5 expressing non-small cell lung cancer cells resistant to antibody-drug conjugates [J].

Kim, Ye-Jin ;

Li, Wei ;

Zhelev, Doncho V. V. ;

Mellors, John W. W. ;

Dimitrov, Dimiter S. S. ;

Baek, Du-San .

FRONTIERS IN ONCOLOGY, 2023, 13

[27] B7-H3 Chimeric Antigen Receptor Redirected T Cells Target Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma [J].

Zi, Zhenguo ;

Zhao, Haihong ;

Wang, Huanyu ;

Ma, Xiaojing ;

Wei, Fang .

CANCERS, 2020, 12 (12) :1-14

[28] PD-L1/PD-1 blockage enhanced the cytotoxicity of natural killer cell on the non-small cell lung cancer (NSCLC) by granzyme B secretion [J].

Qiao, Duan-Rui ;

Cheng, Jun-Ya ;

Yan, Wei-Qun ;

Li, Hai-Jun .

CLINICAL & TRANSLATIONAL ONCOLOGY, 2023, 25 (08) :2373-2383

[29] Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer [J].

Kaichao Feng ;

Yelei Guo ;

Hanren Dai ;

Yao Wang ;

Xiang Li ;

Hejin Jia ;

Weidong Han .

Science China(Life Sciences) , 2016, (05) :468-479

[30] Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer [J].