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  3. The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies

The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies

  • Front Immunol. 2022 May 26:13:808347. doi: 10.3389/fimmu.2022.808347.
Diwei Zheng 1 2,  Xindong Wang 3,  Lin Cheng 3,  Le Qin 1,  Zhiwu Jiang 1,  Ruocong Zhao 4,  Yao Li 1 2,  Jingxuan Shi 1 2,  Qiting Wu 1,  Youguo Long 1,  Suna Wang 1,  Zhaoyang Tang 5 6,  Wei Wei 7,  Jie Yang 8,  Yangqiu Li 9,  Hongsheng Zhou 10,  Qifa Liu 10,  Pentao Liu 11,  Xinwen Chen 1,  Yao Yao 1,  LiHua Yang 12,  Peng Li 1 2 3 4
Affiliations

Affiliations

  • 1 China-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, China.
  • 2 University of Chinese Academy of Sciences, Beijing, China.
  • 3 Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China.
  • 4 Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences, Hong Kong, Hong Kong SAR, China.
  • 5 Guangdong Zhaotai In vivo Biomedicine Ltd., Guangzhou, China.
  • 6 Guangdong Zhaotai Cell Biology Technology Ltd., Foshan, China.
  • 7 Guangdong Cord Blood Bank, Guangzhou, China.
  • 8 Guangdong Women and Children Hospital, Guangzhou, China.
  • 9 Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.
  • 10 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 11 School 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, China.
  • 12 Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
PMID: 35693763 DOI: 10.3389/fimmu.2022.808347
Abstract

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.

Keywords

ATLL; CAR T cells; CCR8; T cell malignancy; TAX.

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