嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T)疗法目前已应用于血液肿瘤的治疗,前期研究发现CD74在白血病患者白血病干细胞中高表达,为了探索其对白血病细胞的杀伤作用,通过CD74 CAR表达载体的构建、慢病毒载体的包装及T细胞的感染,制备CD74 CAR-T细胞.利用体外杀伤实验及细胞因子的释放检测确定CAR-T细胞对CD74+的白血病细胞的特异性杀伤作用.结果显示,CD74 CAR-T分别与CD74+的THP-1及CD74-的K562白血病细胞共培养时,THP-1细胞可被清除,而对CD74-的K562细胞无明显杀伤作用.CD74 CAR-T细胞可被CD74+的THP-1细胞有效激活,通过细胞因子释放途径有效杀伤白血病细胞.研究成功构建了靶向CD74+的白血病细胞的 CAR-T细胞,为白血病的免疫治疗提供了新的靶点和免疫治疗策略.
Anti-leukemia Effect of Chimeric Antigen Receptor T Cells Targeting CD74 Positive Leukemia Cells
Chimeric antigen receptor T cell(CAR-T)therapy has been used in treatment of hematological malignancy.The previ-ous study has found that CD74 is highly expressed in leukemia stem cells.In order to explore its killing effect on leukemia cells,CD74 CAR-T cells were prepared by constructing CD74 CAR expression vector,packing lentivirus and infecting T cells.The spe-cific killing effect of CAR-T cells on CD74 positive leukemia cells was determined by killing experiment in vitro and cytokine re-lease detection.The results showed that when CD74 CAR-T was co-cultured with CD74+THP-1 or CD74-K562 leukemia cells,THP-1 cells could be eliminated,but there was no obvious killing effect on CD74-K562 cells.CD74+THP-1 cells could effective-ly activate CAR-T cells,and activated anti-CD74 CAR-T cells could effectively leukemia cells through cytotoxicity pathways.The study successfully established CAR-T cells targeting CD74+leukemia cells,thus providing new target and immunotherapy strategy for leukemia immunotherapy.
chimeric antigen receptor T cellCD74acute myeloid leukemialeukemia stem cell
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维普
