VEGFR-1特异性的基因工程化T淋巴细胞的抗肿瘤作用及机制研究

项目名称： VEGFR-1特异性的基因工程化T淋巴细胞的抗肿瘤作用及机制研究

项目编号： No.81201789

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 王玮

作者单位： 四川大学

项目金额： 23万元

中文摘要： 嵌合型抗原受体（chimeric antigen receptor， CAR）基因工程化T淋巴细胞能够特异识别肿瘤抗原，产生对肿瘤细胞的靶向杀伤活性。目前，多种靶向识别肿瘤抗原的CAR修饰的T淋巴细胞已经进入临床试验阶段。本项目首次设计了针对血管内皮细胞生长因子受体1（VEGFR-1）的CAR并利用非病毒载体手段实现了T淋巴细胞的基因修饰，得到了一种具有VEGFR-1靶向识别能力的T淋巴细胞（V1-CAR T）。在前期的工作中我们已经证实，V1-CAR T细胞能够对高表达VEGFR-1的肿瘤细胞及激活的血管内皮细胞产生特异的细胞杀伤活性，在体内也能够抑制肿瘤的形成及转移。在此基础上，我们拟对V1-CAR T细胞对肿瘤新生血管的破坏作用及其抗肿瘤作用的机制进行深入分析，阐明CAR的亲和力及VEGFR-1的表达水平对抑瘤作用的影响机制，为V1-CAR T的临床应用提供实验依据。

中文关键词： 血管内皮细胞生长因子受体1；嵌合型抗原受体T细胞；血管形成；肿瘤免疫治疗；

英文摘要： Lymphocytes genetically modified with chimeric antigen receptor (CAR) obtain specificity of tumor associated antigen and induce cytotoxicity to cancer cells.Currently,plentys of CAR modified T cells are clinically used to treat tumors. In our study, we firstly designed a CAR targeting to vascular endothelial growth factor 1 (VEGFR-1) and genetically modifed T cells, then we obtained the T cells with VEGFR-1 specificity (V1-CAR T). In our previous study, the cytotoxicity of V1-CAR T cells to cancer cells with high expression level of VEGFR-1 and activatied vascular endothelial cells has been determined. V1-CAR T cells also delayed the formation and metastasis of tumor, in vivo. Based on the previous data, we plan to further investigate the mechanism by which V1-CAR T cells break the neo-vasculature of tumor and inhibit the growth of different cancers. The relationship between expression level of VEGFR-1, affinity of the CAR and the efficacy of tumor inhibition is to be elucidated. This study will provide fundations for the potential clinical usage of the genetically modified T cells.

英文关键词： VEGFR-1；CAR-T；angiogenesis；cancer immunotherapy；