嵌合抗原受体（CAR）-T细胞在B细胞肿瘤的免疫治疗中取得了很好的效果，但由于高度异质性的，缺乏像CD19分子一样特异性的治疗靶点，CAR-T细胞在实体瘤的治疗中一直无实质性进展。γδT细胞受体，能直接识别完整抗原，且对实体瘤识别谱广，能有效的弥补CAR-T细胞治疗实体瘤上的不足。鉴于此，本研究拟基于前期已验证的，具有肿瘤结合特异性CDR3δ序列（OT3和GTM），用包含该序列的单链γδTCR结构，作为CAR分子的胞外区，构建CARγδ-T细胞；并在体内外实验中联合多种辅助策略，观察CARγδ-T细胞对包括非小细胞肺癌、肝癌、胃癌、卵巢癌在内的实体瘤的治疗效果。此外，我们还将利用高通量免疫组库测序技术，继续筛选验证更多的具有肿瘤结合特异性和亲和力的CDR3δ序列。该研究是结合γδT细胞和CAR-T细胞的肿瘤免疫治疗新的尝试，将为解决实体肿瘤的CAR-T细胞过继免疫治疗提供参考和建议。

Chimeric antigen receptor (CAR) -T cells has made a major breakthrough in tumor immunotherapy in the treatment of B cell lymphocytoma . However, so far, CAR-T cells in the treatment of solid tumors is still no substantive progress, mainly due to the lack of specific therapeutic target molecules like CD19 in highly heterogeneous solid tumors. Without MHC restriction, gamma delta T cell receptor (TCRγδ) recognizes a broad spectrum of solid tumor antigens directly in a manner similar to the antibody, and can effectively compensate for the lack of CAR-T cells in the treatment of solid tumors. In this study, we tried to combine the advantages of TCRγδ in tumor antigen recognition and classic CAR-T cells. First CARγδ -T cells with tumor specific CDR3δ sequence OT3 and GTM would be constructed that the extracellular molecular structure of CARs were replaced by single chain TCRγδ molecules based on above CDR3δ sequences; And combined with a variety of strategies that beneficial for cell activation, invasion and to eliminate the microenvironment of immune suppression, the therapeutic effects of CARγδ-T cells of solid tumor in vivo were observed. In addition, by the high-throughput immune repertoire sequencing technology, we tried to obtain new tumor-specific CDR3δ sequences that dominant in tumor patients and specific binding to tumor cells. The study is a new attempt for combination of γδ T cells and CAR-T cells in tumor immunotherapy. The results would provide reference and suggestions for CAR-T cells adoptive immunotherapy to solid tumors.