基于磁性和光学多模态影像探针标记效应T淋巴细胞免疫治疗脑胶质瘤的在体示踪研究

脑胶质瘤术后残余肿瘤的放化疗效果欠佳是胶质瘤高复发的主要原因。细胞免疫治疗可能是根除术后残余病灶最具前途的方法。体内胶质瘤细胞的免疫逃逸使T淋巴细胞无法致敏，而肿瘤细胞体外致敏T淋巴细胞注入体内有望杀灭残余肿瘤达到根治目的。现阶段缺乏在活体状态下对效应T淋巴细胞治疗效果的评价方法。通过无创分子影像技术对致敏效应T淋巴细胞示踪可实现其对肿瘤归巢、分化和治疗效果的可视化，并实现影像指导下的免疫治疗疗效评估。本课题拟通过经静脉注入经磁性/光学多模态影像探针标记的体外致敏效应T淋巴细胞至GL261胶质瘤荷瘤小鼠体内，利用7T MR和近红外荧光成像对T淋巴细胞进行在体示踪。通过与病理切片对照分析，揭示该方法在体示踪细胞免疫治疗胶质瘤的灵敏度和特异性；利用功能MR方法监测细胞免疫的疗效。该项目为评估效应T淋巴细胞对胶质瘤疗效提供影像学基础。对指导细胞免疫进行脑胶质瘤残余肿瘤的个体化生物治疗有重要意义。

The main reason of high recurrence of glioma is that the radiotherapy and chemotherapy to the post-operative remnant tumor are not effective,while immunotherapy may be the most prospect method for complete cure of the remnant lesion.T lymph cells cannot be immuned in vivo due to immune escape of glioma cells, but T lymph cells immuned by tumor cells in vitro maybe eliminate the remnant glioma lesions, which will achieve the aim of complete cure.But on the present time,there is no effective method for evaluating the treatment effect of T lymph cells in vivo.Through molecular imaging technology tracking the immuned T lymph cells, we can make it visualable for these T lymph cells to home to tumor,differentiate,and treat the tumor.Furthermore,It will realize evaluation of the effect of immuotherapy under guidance of imaging. This item is designed to do following things:To inject T lymph cells,which are immuned in vitro and marked with magnetic and optical multimodel molecular probe,to the body of GL261 glioma mice via vein, to tracking the T lymph cells in vivo with 7 Tesla and near-infrared fluorescence ,to explore the imaging sensitivity and specificity on tracking the immunotherapy in vivo through comparing with pathology.On the other hand, to supervise in real time the effect of cellular immunotherapy with functional MR. This item will provid imaging foundation for objective evaluation of T lymph cells on treatment of glioma.It will be of important research and clinical meaning to guide private biological treatment on remnant glioma with cellular immunotherapy.