靶向CD74的嵌合抗原受体T细胞的抗白血病细胞作用研究  

Anti-leukemia Effect of Chimeric Antigen Receptor T Cells Targeting CD74 Positive Leukemia Cells

作　　者：刘一鸣 谢乐灵 邢海燕 唐克晶 王敏 饶青 LIU Yiming;XIE Leling;XING Haiyan;TANG Kejing;WANG Min;RAO Qing(State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Tianjin Key Laboratory of Cell Therapy for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China;Tianjin Institutes of Health Science,Tianjin 301600,China)

机构地区：[1]中国医学科学院血液病医院(中国医学科学院血液学研究所)北京协和医学院,血液与健康全国重点实验室,国家血液系统疾病临床医学研究中心,天津市血液病细胞治疗研究重点实验室,细胞生态海河实验室,天津300020 [2]天津医学健康研究院,天津301600

出　　处：《生物技术进展》2024年第3期501-505,共5页Current Biotechnology

基　　金：国家自然科学基金项目(81770106)。

摘　　要：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。Chimeric antigen receptor T cell(CAR-T)therapy has been used in treatment of hematological malignancy.The previous 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 specific killing effect of CAR-T cells on CD74 positive leukemia cells was determined by killing experiment in vitro and cytokine release 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 effectively 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.

关 键 词：嵌合抗原受体修饰的T细胞 CD74 急性髓系白血病 白血病干细胞 

分 类 号：Q291[生物学—细胞生物学] R733.71[医药卫生—肿瘤]