CELL INTELLIGENCE · 肿瘤细胞治疗研究

Genetic modification of T cells to express chimeric antigen receptors (CAR, CAR-T cells) enable them to recognize the specific antigen on tumor surface and then eliminate the tumor. T lymphocyte ion channels such as Kv1.3, KCa3.1 and CRAC influence T cell activation and proliferation by regulating Ca2+ signaling, as well as other effector functions such as cytokine release, migration and even target cell killing. Here we established two CAR cell lines (using CEM T cell line and primary T cells) recognizing CD19 antigen on surface of Raji B and human breast cancer MCF-7 expressing CD19 cell lines. First, we exposed that KCa3.1 and Kv1.3 functional expressions of CEM cells were comparable to those in T cells, which demonstrated their suitability for primary T cell mimics. Next, we studied the tumor cell killing efficiency of CAR-T and CEM-CAR cells in monolayer and 3D spheroid tumor models. We could show that CAR expressing cells specifically eliminate tumor cells regardless of tumor models. Furthermore, the application of Kv1.3 (Vm24) and KCa3.1 (TRAM34) inhibitors significantly improved the tumor eradication efficiency for both CEM-CAR and CAR-T cells in spheroids, however, the infiltration rate was not influenced upon addition of antagonists. We could conclude that modification of Kv1.3 and KCa3.1 ion channels could contribute to a more effective immunotherapy of solid tumor.