CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma

BMC Medicine

Research Article

Yong Li¹  Lijuan Han²  Jianxiang Zhang²  Zhaoming Li³  Mingzhi Zhang³  Hongwen Li³  Jiwei Li³  Jiazhuo Wu⁴  Yuyang Gao⁴  Wenting Song⁴  Zhuangzhuang Shi⁴ 

[1] Department of Medicine, Baylor College of Medicine, Houston, TX, USA;Department of Oncology, Jianshendong Rd., The First Affiliated Hospital of Zhengzhou University, No. 1, 450052, Zhengzhou, Henan Province, China;Department of Oncology, Jianshendong Rd., The First Affiliated Hospital of Zhengzhou University, No. 1, 450052, Zhengzhou, Henan Province, China;State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China;Department of Oncology, Jianshendong Rd., The First Affiliated Hospital of Zhengzhou University, No. 1, 450052, Zhengzhou, Henan Province, China;State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China;Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan, China;

关键词: CD38;    LMP1;    CAR-T;    Tandem;    Immunotherapy;    NKTCL;   

DOI  :  10.1186/s12916-023-03040-0

 received in 2023-04-14, accepted in 2023-08-18,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundNatural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies.MethodsIn this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry.ResultsThe four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated and produce inflammatory cytokines in a target-dependent manner. In vivo tests showed that the CAR-T cells exhibited significant antitumour effects in a xenotransplanted NKTCL mouse model.ConclusionsIn summary, four CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo. These results indicated the effective therapeutic promise of CD38 and LMP1 CAR-T cells in NKTCL.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 6

41512_2023_153_Article_IEq65.gif

Fig. 4