AUTHOR=Zheng Diwei , Wang Xindong , Cheng Lin , Qin Le , Jiang Zhiwu , Zhao Ruocong , Li Yao , Shi Jingxuan , Wu Qiting , Long Youguo , Wang Suna , Tang Zhaoyang , Wei Wei , Yang Jie , Li Yangqiu , Zhou Hongsheng , Liu Qifa , Liu Pentao , Chen Xinwen , Yao Yao , Yang LiHua , Li Peng TITLE=The Chemokine Receptor CCR8 Is a Target of Chimeric Antigen T Cells for Treating T Cell Malignancies JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.808347 DOI=10.3389/fimmu.2022.808347 ISSN=1664-3224 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.