Effect of IL7 and/or Flt3L expression of CAR T cells on gene expression and TCR diversity in EGFRvIII heterogenous mouse glioblastoma with 0.5 Gy irradiation

We investigated the effect of intratumoral delivery of IL7 and/or Flt3L expressing CAR T cells in 50% EGFRvIII positive CT2A tumors treated with 0.5 Gy irradiation. We performed gene expression analysis of the tumor bearing hemisphere using RNA-seq. Female C56BL/6 mice were given 50% CT2A-huEGFRvIII-Luc and 50% CT2A-GFP-Luc cells intracranially on day 0. On day 6, mice underwent total body irradiation and the following day 2x10^6 CAR T cells were intracranially delivered with or without poly(I:C) (pIC). Gene expression was assessed on day 14.

本研究探究了经0.5 Gy放射照射的、50%细胞为表皮生长因子受体变异体III（EGFRvIII）阳性的CT2A肿瘤模型中，表达白细胞介素7（IL7）和/或FMS样酪氨酸激酶3配体（Flt3L）的嵌合抗原受体T细胞（CAR T细胞）的瘤内递送效果。我们采用RNA测序（RNA-seq）对荷瘤大脑半球开展基因表达分析。实验于第0天向雌性C56BL/6小鼠颅内接种50% CT2A-huEGFRvIII-Luc与50% CT2A-GFP-Luc细胞；第6天时，小鼠接受全身照射，次日于颅内递送2×10^6个CAR T细胞，同时辅以或不辅以聚肌胞苷酸（poly(I:C)，简称pIC）；最终于第14天评估基因表达情况。