高浓度钾离子对嵌合抗原受体CAR-T细胞扩增及功能的影响  

Effects of high potassium concentration to the expansion and cytotoxicity of chimeric antigen receptor T cells

作　　者：章崇祺 常昊宛 王欢禹 马小京 魏芳 ZHANG Chongqi;CHANG Haowan;WANG Huanyu;MA Xiaojing;WEI Fang(Sheng Yushou Center of Cell Biology and Immunology,School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,China)

机构地区：[1]上海交通大学生命科学技术学院盛毓绶细胞与免疫学研究中心,200240

出　　处：《免疫学杂志》2021年第8期686-691,共6页Immunological Journal

摘　　要：目的探索高浓度钾离子条件对嵌合抗原受体(CAR)-T细胞的体外培养及杀伤能力的影响。方法体外使用间皮素特异靶向的嵌合抗原受体Meso-CAR改造T细胞,在激活或扩增阶段使用高浓度钾离子培养基,通过细胞计数、流式细胞术分析CD4^(+)和CD8^(+)T细胞扩增及PD-1细胞表面表达等情况,并通过荧光素酶检测细胞杀伤能力。结果高浓度钾离子不影响Meso-CAR CD4^(+)和CD8^(+)T细胞体外扩增,但可显著提升CAR-T细胞激活后表面PD-1的表达,并显著提高T细胞体外的杀伤能力。结论高浓度钾离子可以优化CAR-T细胞的体外改造并提高其杀伤能力。This study was designed to investigate the effects of high K^(+)concentration on the expansion and cytotoxicity of chimeric antigen receptor(CAR)T cells in vitro.T cells were modified by mesothelin specific CAR(Meso-CAR),and then cultured with high K^(+)concentration during activation or/and amplification.Cell counting and flow cytometry analysis were performed to evaluate CD4^(+)and CD8^(+)T cell proliferation,and PD-1 expression on the cell surface.Luciferase-based cytotoxicity assay was performed to measure the cytotoxicity of CAR-T cells.Data showed that high K^(+)concentration culturing condition did not influence the proliferation of Meso-CAR CD4^(+)and CD8^(+)T cells,but significantly enhanced PD-1 expression and cytotoxicity of CAR-T cells.In conclusion,high K^(+)concentration can be utilized to optimize in vitro modifications and enhance the cytotoxicity of CAR-T cells.

关 键 词：嵌合抗原受体T细胞 PD-1 高浓度钾离子 

分 类 号：R392.1[医药卫生—免疫学]