磁性纳米粒子对嵌合抗原受体T细胞治疗的协同作用

Synergistic effects of magnetic nanoparticles for chimeric antigen receptor T cell therapy

目的探索纳米磁性粒子对肿瘤免疫治疗的细胞增殖、活化、细胞毒性和分化的影响, 以期为进一步提高肿瘤免疫细胞治疗效果提供新的治疗策略。方法制备氧化铁磁性纳米粒子SPIONCitrate, 在体内外实验中将磁性纳米粒子直接与CD8(+)T细胞和CD19-CAR-T细胞混合培养, 观察免疫细胞表型、增殖和对Raji-luc细胞杀伤作用的影响。结果经过磁性纳米粒子后, CD8(+)T细胞中Tem[CD45RO(+)CD62L(-)]比例增加, Tcm[CD45RO(+)CD62L(+)]比例减少, 在体内外均能提高CD8(+)T细胞的增殖能力, 且能提高CD19-CAR-T细胞的杀伤作用。结论磁性纳米粒子可以直接改变免疫细胞表型, 提高其增殖和杀伤肿瘤细胞的能力。

Objective To explore the effects of magnetic nanoparticles on the proliferation,activation,cytotoxicity,and differentiation of immune cells in tumor therapy,and to provide new therapeutic strategies for further improving the therapeutic effect of cellular immunity.Methods Iron oxide magnetic nanoparticles(SPIONCitrate)were prepared and directly mixed with CD8(+)T cells and CAR-T cells to observe the effects of immune cell phenotype,proliferation,and killing effect on Raji-luc cells in both in vitro and in vivo experiments.Results After passing through magnetic nanoparticles,the proportion of Tem(CD45RO(+)CD62L(-))and Tcm(CD45RO(+)CD62L(+))in CD8(+)T cells increased,and the proportion of Tcm(CD45RO(+)CD62L(+))decreased,which improved the proliferation ability of CD8(+)T cells both in vivo and in vitro,and also enhanced the killing effect of CD19-CAR-T cells.Conclusion Magnetic nanoparticles can directly alter the phenotype of immune cells,enhance their ability to proliferate and kill tumor cells.