Endoglin核酸适配体修饰的肿瘤/DC杂交细胞囊泡疫苗靶向抗肿瘤研究

针对目前肿瘤/DC杂交细胞疫苗靶向治疗有待提高的难题，本课题组前期进行预实验：将肿瘤/DC杂交细胞制备成纳米囊泡，该囊泡能够表达DC表面的共刺激分子。据此提出将肿瘤/DC杂交细胞疫苗制备成既能刺激T细胞活化又能载药的纳米囊泡疫苗。设想在纳米囊泡疫苗表面修饰本项目组前期筛选得到的可以与肿瘤新生血管内皮细胞特异性结合的Endoglin核酸适配体，然后包裹能够趋化T细胞的趋化因子CXCL9，最终制备成既能靶向到肿瘤新生血管和肿瘤局部，又能诱生肿瘤特异性CTL并趋化CTL到肿瘤局部的靶向性纳米囊泡疫苗。在体外验证其靶向性及诱生的CTL杀伤能力，然后输入荷人肝癌SCID小鼠体内，探索其体内靶向抗肝癌作用及其可能的分子免疫学机制。若本项目能顺利实施，将为DC疫苗的研发带来新的突破，具有重要的理论意义和广泛应用前景。

Aiming at solving the problems of targeted therapy of tumor / DC hybrid cell vaccines, our research group conducted preliminary experiments in advance: preparing tumor / DC hybrid cells as nanovesicles, and the results suggested that they had expressed co-stimulatory molecules on the surface of DCs. Based on this, we propose to prepare a tumor / DC hybrid cell vaccine as a nanovesicle vaccine that can both stimulate T cell activation and load drugs. It is envisaged to modify the previously selected Endoglin nucleic acid aptamer, which can be specifically bound to tumor neovascular endothelial cells, on the surface of nanovesicle vaccine, and then encapsulate the chemokine CXCL9 that can chemotactic T cells. Finally, a targeted nanovesicle vaccine that can target tumor neovascularization and tumor localities, and induce tumor-specific cytotoxic T lymphocytes（CTL）and chemotactic CTL to tumor localities is prepared. The targeting and induced CTL killing ability will be verified in vitro, and then introduced into SCID mice bearing human liver cancer to explore its anti-cancer effect in vivo and its possible molecular immunological mechanism. If this project can be successfully implemented, it will bring new breakthroughs to the research and development of DC vaccines, which will have important theoretical significance and broad application prospects.