嵌合抗原受体（CAR）是模拟T细胞受体功能的人工受体，近年来利用CAR修饰的T细胞治疗肿瘤的研究备受关注。一些临床试验已取得较好疗效，但仍有很多问题亟待解决，其中两个最为关键，一是确定有效的治疗靶点，二是降低CAR的免疫原性。 组织因子（TF）在恶性肿瘤细胞及新生肿瘤血管内皮细胞高表达，已被证实为多个肿瘤的有效治疗靶点。申请者的前期研究证明TF在肺癌细胞中高表达，是肺癌治疗的有效靶点；凝血因子VII的轻链（lFVII）能有效识别TF，且分子量小，无免疫原性，是TF的理想识别结构域。本项目拟在前期研究基础上，构建以TF为靶点，lFVII为靶点识别结构域的CAR，用其修饰T细胞，通过体内外实验研究该CAR修饰的T细胞对肺癌的治疗效果，并阐明其相关机制，为CAR修饰的T细胞应用于临床肺癌治疗提供理论和实验依据。

The chimeric antigen receptor (CAR) is an artificial T cell receptor that simulates the physiological functions of the native T cell receptor (TCR). CAR-modified T cells for cancer therapy has been extensively studied in recent years. Some clinical trials have shown significant effect. However, there are still some problems to be solved. Two of them are most critical. One is determining effective tumor target, another is decreasing the immunogenicity of CAR to prolong the survival of CAR-modified T cells in vivo. Tissue factor (TF) is overexpressed in malignant tumor cells and angiogenic tumor vascular endothelial cells, and had been proved an effective target for cancer therapy. The results of our previous research have demonstrated that tissue factor is overexpressed in lung cancer cells, is an effective target for lung cancer therapy.Factor VII is the natural ligand of TF. We have proved that the light chain of factor VII (lFVII) is an ideal targeting molecule of TF. In this project, we will constructed a novel CAR which contains lFVII as the targeting domain and targets to TF, and study the therapeutic effect and mechanisms of the CAR-modified T cells for lung cancer. This study will provide theoretical and experimental basis for the CAR-modified T cells' clinical application for lung cancer.