近年来，作为精准细胞免疫治疗方法中最有希望一种的TCR-T在几种恶性肿瘤治疗中的应用取得了显著的治疗效果，但对大部分实体瘤难以发挥疗效。本研究将以提高TCR-T对实体瘤疗效为目的，着力于提高TCR-T对实体瘤的浸润能力以及降低肿瘤微环境的免疫抑制效应。首先，为增强浸润能力， 一方面利用穿膜免疫调节肽DSPE-PEG-DP7对T细胞进行活化增强其实体瘤浸润能力和免疫效应，并对其机制进行研究；一方面拟探索建立iPSC体外诱导NY-ESO-1 TCR-T的体系，诱导产生具有更强浸润能力TCR-T。其次，为降低肿瘤微环境的免疫抑制效应，拟利用Crisper/Cas9 系统敲除TCR-T中的PD-1基因，结合iPSC诱导TCR-T及DSPE-PEG-DP7的促进作用，以期达到多重促进综合提升TCR-T对实体瘤疗效的作用。籍此，探索提高TCR-T对实体瘤疗效的途径，为发展异体通用型TCR-T提供参考。

In recent years, as one the of most promising treatment in precision cell immunotherapies, TCR-T has shown remarkable therapeutic effects in the treatment of some kind of malignant tumors, but it is still difficult to exert effects on most solid tumors. This study will focus on improving the efficacy of TCR-T on solid tumors, focusing on improving the invasive ability of TCR-T on solid tumors and reducing the immunosuppressive effects of tumor microenvironment. Firstly, in order to enhance the infiltration ability, on the one hand, the transmembrane immunoregulatory peptide DSPE-PEG-DP7 was used to activate T cells to enhance the infiltration ability and immune effect of solid tumors, and the mechanism was studied. On the one hand, it was proposed to establish the in vitro iPSC- NY-ESO-1TCR-T induction system, to induce TCR-T with a stronger infiltration capacity. Secondly, in order to reduce the immunosuppressive effect of tumor microenvironment, it is proposed to use the Crisper/Cas9 system to knock out the PD-1 gene in TCR-T, and combine with iPSC-TCR-T and DSPE-PEG-DP7 achieve multiple enhance effects on solid tumors. Therefore, exploring ways to improve the efficacy of TCR-T on solid tumors will also provide a reference for the development of allogeneic universal TCR-T cell therapy products.