嵌合抗原受体（CAR）修饰T细胞为肿瘤免疫治疗带来新的希望，它赋予T细胞靶向杀伤活性，克服肿瘤局部免疫抑制微环境，改善宿主免疫耐受状态。然而，这种"超自然"T细胞的调控是临床基因和细胞治疗需要解决的关键问题。本课题设计可诱导的自杀基因iCaspase9，与肿瘤特异性抗原EGFRvIII的CAR相结合，建立CAR修饰T细胞的调控模型；体外试验探讨iCaspase9诱导CAR T细胞凋亡、理想治疗潜质的T细胞亚群、最佳的T细胞活化信号；动物实验通过CAR T细胞条件性消融模型、移植物抗宿主病模型、肿瘤原位移植模型探索CAR修饰T细胞肿瘤免疫治疗的调控性、安全性、有效性，可能的分子机制和应对策略。EGFRvIII是脑胶质瘤等多种恶性肿瘤表达率很高的肿瘤特异性抗原，肿瘤靶向治疗理想的分子靶点，本研究为肿瘤免疫治疗新策略提供实验依据、临床基因治疗提供调控手段、脑胶质瘤等恶性肿瘤探索新的治疗方法。

Chimeric Antigen Receptor-Engineered T Cells bring new hope for tumor immunotherapy, which endow T cells target cytotoxicity, overcome local suppressive microenvironment of tumor, break immune tolerance of host. However, controlling of such supernatural T cells is a key issue in clinical gene and cellular therapy. We design an inducible suicide gene Caspase 9, combined with EGFRvIII CAR, establish controllable model of Chimeric Antigen Receptor-Engineered T Cells. Experiments in vitro will explore inducible apoptosis of CAR T cells, ideal T cell subgroups of therapeutic potential, best activation signal of T cells. Conditional CAR T ablation model, graft-versus-host disease model, in situ tumor engraft model will be used to discuss the control, safety and effect of CAR-based immunotherapy. EGFRvIII (Epidermal Growth Factor variant III) is a tumor specific antigen highly expressed in glioma and other malignant tumors, a promising molecular marker of tumor target therapy. Our study will provide experimental data for this new strategy of immunotherapy, controlling tool for clinical gene therapy, and new therapy for glioma.