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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.01089/full |
| _version_ | 1818613550875148288 |
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| author | Shuo Yang Shuo Yang Bihui Cao Guangyu Zhou Guangyu Zhou Lipeng Zhu Lipeng Zhu Lu Wang Li Zhang Hang Fai Kwok Hang Fai Kwok Zhenfeng Zhang Qi Zhao Qi Zhao |
| author_facet | Shuo Yang Shuo Yang Bihui Cao Guangyu Zhou Guangyu Zhou Lipeng Zhu Lipeng Zhu Lu Wang Li Zhang Hang Fai Kwok Hang Fai Kwok Zhenfeng Zhang Qi Zhao Qi Zhao |
| author_sort | Shuo Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T16:03:54Z |
| format | Article |
| id | doaj.art-ea7a89cc80c54d79b8805e2fb22c7860 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-16T16:03:54Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-ea7a89cc80c54d79b8805e2fb22c78602022-12-21T22:25:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-07-011110.3389/fphar.2020.01089573445Targeting B7-H3 Immune Checkpoint With Chimeric Antigen Receptor-Engineered Natural Killer Cells Exhibits Potent Cytotoxicity Against Non-Small Cell Lung CancerShuo Yang0Shuo Yang1Bihui Cao2Guangyu Zhou3Guangyu Zhou4Lipeng Zhu5Lipeng Zhu6Lu Wang7Li Zhang8Hang Fai Kwok9Hang Fai Kwok10Zhenfeng Zhang11Qi Zhao12Qi Zhao13Cancer Centre, Faculty of Health Sciences, University of Macau, Macau, ChinaInstitute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau, ChinaDepartment of Radiology, Translational Medicine Center and Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenviroment, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaCancer Centre, Faculty of Health Sciences, University of Macau, Macau, ChinaInstitute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau, ChinaCancer Centre, Faculty of Health Sciences, University of Macau, Macau, ChinaInstitute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau, ChinaDepartment of Radiology, Translational Medicine Center and Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenviroment, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesCancer Centre, Faculty of Health Sciences, University of Macau, Macau, ChinaInstitute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau, ChinaDepartment of Radiology, Translational Medicine Center and Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenviroment, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaCancer Centre, Faculty of Health Sciences, University of Macau, Macau, ChinaInstitute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau, ChinaChimeric 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.https://www.frontiersin.org/article/10.3389/fphar.2020.01089/fullB7-H3chimeric antigen receptorNK-92immune checkpointnatural killer cell |
| spellingShingle | Shuo Yang Shuo Yang Bihui Cao Guangyu Zhou Guangyu Zhou Lipeng Zhu Lipeng Zhu Lu Wang Li Zhang Hang Fai Kwok Hang Fai Kwok Zhenfeng Zhang Qi Zhao Qi Zhao Targeting B7-H3 Immune Checkpoint With Chimeric Antigen Receptor-Engineered Natural Killer Cells Exhibits Potent Cytotoxicity Against Non-Small Cell Lung Cancer Frontiers in Pharmacology B7-H3 chimeric antigen receptor NK-92 immune checkpoint natural killer cell |
| title | Targeting B7-H3 Immune Checkpoint With Chimeric Antigen Receptor-Engineered Natural Killer Cells Exhibits Potent Cytotoxicity Against Non-Small Cell Lung Cancer |
| title_full | Targeting B7-H3 Immune Checkpoint With Chimeric Antigen Receptor-Engineered Natural Killer Cells Exhibits Potent Cytotoxicity Against Non-Small Cell Lung Cancer |
| title_fullStr | Targeting B7-H3 Immune Checkpoint With Chimeric Antigen Receptor-Engineered Natural Killer Cells Exhibits Potent Cytotoxicity Against Non-Small Cell Lung Cancer |
| title_full_unstemmed | Targeting B7-H3 Immune Checkpoint With Chimeric Antigen Receptor-Engineered Natural Killer Cells Exhibits Potent Cytotoxicity Against Non-Small Cell Lung Cancer |
| title_short | Targeting B7-H3 Immune Checkpoint With Chimeric Antigen Receptor-Engineered Natural Killer Cells Exhibits Potent Cytotoxicity Against Non-Small Cell Lung Cancer |
| title_sort | targeting b7 h3 immune checkpoint with chimeric antigen receptor engineered natural killer cells exhibits potent cytotoxicity against non small cell lung cancer |
| topic | B7-H3 chimeric antigen receptor NK-92 immune checkpoint natural killer cell |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.01089/full |
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