Frontiers in Immunology (May 2022)

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

  • 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

DOI
https://doi.org/10.3389/fimmu.2022.808347
Journal volume & issue
Vol. 13

Abstract

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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.

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