肿瘤细胞治疗研究
英文原题：CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma.
四种 CAR-T 细胞系在体外和体内均对 NKTCL 细胞表现出显著的细胞毒性。
背景：自然杀伤/T 细胞淋巴瘤（NKTCL）是一种侵袭性强、预后差的淋巴瘤。嵌合抗原受体转导 T（CAR-T）细胞疗法已成为治疗血液系统恶性肿瘤的一种有前景的免疫疗法。方法：研究制备了 4 种 CAR-T 细胞：CD38-CAR、LMP1-CAR、CD38-LMP1 串联 CAR 1 和 CD38-LMP1 串联 CAR 2，并在体外和体内评估其对 NKTCL 细胞的作用。采用流式细胞术检测 CAR-T 细胞表达的 T 细胞活化标志物和产生的细胞因子。结果：4 种 CAR-T 细胞均能有效清除恶性 NKTCL 细胞，并以靶标依赖的方式活化和产生炎性细胞因子。体内实验显示，CAR-T 细胞在 NKTCL 异种移植小鼠模型中具有显著抗肿瘤效果。结论：总体而言，4 种 CAR-T 细胞系在体内和体外均对 NKTCL 细胞表现出显著细胞毒性。这些结果表明，CD38 和 LMP1 CAR-T 细胞对 NKTCL 具有有效治疗的潜力。
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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