[摘要] 目的：探讨靶向CD19 抗原的CAR-NK-92MI和CAR-CD19-T 细胞对套细胞淋巴瘤（mantle cell lymphoma，MCL）的体外杀伤作用。方法：利用近年来在B细胞急性淋巴细胞白血病（B-lineage acute lymphoblastic leukemia, B-ALL）临床试验中获得的成功嵌合抗原受体基因修饰的T（CAR-T 细胞）技术，针对MCL高表达CD19 抗原的情况，分别构建了靶向CD19 抗原的CAR-CD19-T和CAR-NK-92MI细胞，运用LDH释放法检测两者对MCL细胞的体外杀伤作用，另外通过流式细胞术对其杀伤作用进行了验证。结果：相对于对照，无论是CAR-NK-92MI细胞还是CAR-CD19-T 细胞，都对MCL细胞具有极高的杀伤能力（均P <0.01），都对K562-CD19 细胞具有非常高的毒性（均P <0.01），而对K562 细胞基本不起作用。CAR-NK-92MI细胞组MCL细胞的死亡率比对照组高30%~40%，CAR-CD19-T 细胞组MCL细胞的死亡率比对照组高40%~50%。结论：CAR-NK-92MI和CARCD19-T细胞在体外对MCL细胞具有强的特异性杀伤作用。

[Abstract] Objective: To investigate the in vitro cytotoxicity of the chimeric antigen receptor-modified T cells and NK-92MI cells (CAR-NK-92MI cells) and CAR-CD19-T cells against mantle cell lymphoma (MCL). Methods: CAR-T cell technology, successfully obtained in clinical trial of B-lineage acute lymphoblastic leukemia (B-ALL) treatment, was used in this study. In the case of high expression of CD19 antigen in MCL, CAR- CD19-T cells and CAR- CD19-NK-92MI cells targeting CD19 antigen were generated, respectively.Then, their cytotoxicity against MCL cell lines was detected by LDH release assay and the results were verified by flow cytometry.Results: Compared with control group, both CAR-NK-92MI and CAR-CD19-T cells exhibited prominent killing effect against MCL cells（all P<0.01）; in addition, the two CAR cells exhibited high cytotoxicity against K562-CD19 cells but not on K562 cells（all P<0.01）. The death rate of MCL cells from CAR-NK-92MI group was 30%-40% more than that of control group, and the death rate ofMCL from CAR-CD19-T group was 40%-50% more than that of control group. Conclusion: Both CAR-NK-92MI and CAR-CD19-T cells exhibited potent cytotoxicity against MCL cells in vitro.

国家重点研发项目资助（No. 2016YFC1303403 ）