自然杀伤/ T细胞淋巴瘤（NKTCL）是一种预后不良的侵袭性淋巴瘤。嵌合抗原受体转导的T细胞（CAR-T）细胞疗法已成为一种有希望的对抗血液系统恶性肿瘤的免疫治疗策略。本研究构建了四种CAR-T细胞系（CD38-CAR, LMP1-CAR, CD38-LMP1串联CAR 1和CD38-LMP1串联CAR 2）。在体外和体内评价了CAR-T细胞对NKTCL细胞的作用。采用流式细胞术检测了CAR-T细胞对T细胞活化标志物和细胞因子的表达。四种CAR-T细胞系能够有效清除恶性NKTCL细胞。它们能够依赖靶细胞的特异性被激活并产生炎性细胞因子。体内实验显示，CAR-T细胞在移植性NKTCL小鼠模型中展示出显著的抗肿瘤效果。总之，四种CAR-T细胞系在体内外对NKTCL细胞表现出显著的细胞毒性。这些结果表明了CD38和LMP1的CAR-T细胞在NKTCL中具有有效的治疗前景。 © 2023. BioMed Central Ltd., Springer Nature的一部分。

Natural 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.In 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.The 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.In 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.© 2023. BioMed Central Ltd., part of Springer Nature.