The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies
Chimeric antigen receptor (CAR) T cells have been successfully used in the therapy of B cell leukemia and lymphoma, but still have many challenges in their use for treating T cell malignancies, such as the lack of unique tumor antigens, their limitation of T cell expansion, and the need for third pa...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.808347/full |
| _version_ | 1817980935289700352 |
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| author | Diwei Zheng Diwei Zheng Xindong Wang Lin Cheng Le Qin Zhiwu Jiang Ruocong Zhao Yao Li Yao Li Jingxuan Shi Jingxuan Shi Qiting Wu Youguo Long Suna Wang Zhaoyang Tang Zhaoyang Tang Wei Wei Jie Yang Yangqiu Li Hongsheng Zhou Qifa Liu Pentao Liu Xinwen Chen Yao Yao LiHua Yang Peng Li Peng Li Peng Li Peng Li |
| author_facet | Diwei Zheng Diwei Zheng Xindong Wang Lin Cheng Le Qin Zhiwu Jiang Ruocong Zhao Yao Li Yao Li Jingxuan Shi Jingxuan Shi Qiting Wu Youguo Long Suna Wang Zhaoyang Tang Zhaoyang Tang Wei Wei Jie Yang Yangqiu Li Hongsheng Zhou Qifa Liu Pentao Liu Xinwen Chen Yao Yao LiHua Yang Peng Li Peng Li Peng Li Peng Li |
| author_sort | Diwei Zheng |
| collection | DOAJ |
| description | Chimeric antigen receptor (CAR) T cells have been successfully used in the therapy of B cell leukemia and lymphoma, but still have many challenges in their use for treating T cell malignancies, such as the lack of unique tumor antigens, their limitation of T cell expansion, and the need for third party donors or genome editing. Therefore, we need to find novel targets for CAR T cell therapy to overcome these challenges. Here, we found that both adult T-cell leukemia/lymphoma (ATLL) patients and ATLL cells had increased CCR8 expression but did not express CD7. Moreover, targeting CCR8 in T cells did not impair T cell expansion in vitro. Importantly, anti-CCR8 CAR T cells exhibited antitumor effects on ATLL- and other CCR8-expressing T-ALL cells in vitro and in vivo, and prolonged the survival of ATLL and Jurkat tumor-bearing mouse models. In conclusion, these collective results show that anti-CCR8 CAR T cells possess strong antitumor activity and represent a promising therapeutic approach for ATLL and CCR8+ tumors. |
| first_indexed | 2024-04-13T22:59:14Z |
| format | Article |
| id | doaj.art-0dc41a68546941458d6ffed9c0611970 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T22:59:14Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0dc41a68546941458d6ffed9c06119702022-12-22T02:25:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.808347808347The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell MalignanciesDiwei Zheng0Diwei Zheng1Xindong Wang2Lin Cheng3Le Qin4Zhiwu Jiang5Ruocong Zhao6Yao Li7Yao Li8Jingxuan Shi9Jingxuan Shi10Qiting Wu11Youguo Long12Suna Wang13Zhaoyang Tang14Zhaoyang Tang15Wei Wei16Jie Yang17Yangqiu Li18Hongsheng Zhou19Qifa Liu20Pentao Liu21Xinwen Chen22Yao Yao23LiHua Yang24Peng Li25Peng Li26Peng Li27Peng Li28China-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaBioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, ChinaBioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, ChinaChina-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaChina-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaCentre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong SAR, ChinaChina-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaChina-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaChina-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Zhaotai In vivo Biomedicine Ltd., Guangzhou, ChinaGuangdong Zhaotai Cell Biology Technology Ltd., Foshan, ChinaGuangdong Cord Blood Bank, Guangzhou, ChinaGuangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China0Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China0Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China1School of Biomedical Sciences, Stem Cell and Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, ChinaChina-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaChina-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China2Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaChina-New Zealand Joint Laboratory of Biomedine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Chinese Academy of Sciences Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaBioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, ChinaCentre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong SAR, ChinaChimeric antigen receptor (CAR) T cells have been successfully used in the therapy of B cell leukemia and lymphoma, but still have many challenges in their use for treating T cell malignancies, such as the lack of unique tumor antigens, their limitation of T cell expansion, and the need for third party donors or genome editing. Therefore, we need to find novel targets for CAR T cell therapy to overcome these challenges. Here, we found that both adult T-cell leukemia/lymphoma (ATLL) patients and ATLL cells had increased CCR8 expression but did not express CD7. Moreover, targeting CCR8 in T cells did not impair T cell expansion in vitro. Importantly, anti-CCR8 CAR T cells exhibited antitumor effects on ATLL- and other CCR8-expressing T-ALL cells in vitro and in vivo, and prolonged the survival of ATLL and Jurkat tumor-bearing mouse models. In conclusion, these collective results show that anti-CCR8 CAR T cells possess strong antitumor activity and represent a promising therapeutic approach for ATLL and CCR8+ tumors.https://www.frontiersin.org/articles/10.3389/fimmu.2022.808347/fullCCR8TAXATLLT cell malignancyCAR T cells |
| spellingShingle | Diwei Zheng Diwei Zheng Xindong Wang Lin Cheng Le Qin Zhiwu Jiang Ruocong Zhao Yao Li Yao Li Jingxuan Shi Jingxuan Shi Qiting Wu Youguo Long Suna Wang Zhaoyang Tang Zhaoyang Tang Wei Wei Jie Yang Yangqiu Li Hongsheng Zhou Qifa Liu Pentao Liu Xinwen Chen Yao Yao LiHua Yang Peng Li Peng Li Peng Li Peng Li The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies Frontiers in Immunology CCR8 TAX ATLL T cell malignancy CAR T cells |
| title | The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies |
| title_full | The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies |
| title_fullStr | The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies |
| title_full_unstemmed | The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies |
| title_short | The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies |
| title_sort | chemokine receptor ccr8 is a target of chimeric antigen t cells for treating t cell malignancies |
| topic | CCR8 TAX ATLL T cell malignancy CAR T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.808347/full |
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