摘要
目的 研究G42 2肿瘤细胞RNA体外冲击致敏的树突状细胞 (DC)回输诱导体内产生保护性免疫反应及对颅内荷瘤小鼠的免疫治疗效应 ,探讨以DC为基础的疫苗对脑胶质瘤治疗的可行性。方法 提取G42 2胶质母细胞瘤RNA冲击致敏DC制成疫苗 ,分别进行免疫保护和免疫治疗的体内实验 ,以及细胞毒性T淋巴细胞 (CTL)体外诱导及活性检测 ,并与PBS、未经致敏的DC、G42 2肿瘤细胞RNA组进行对照。结果 疫苗能诱导产生针对G42 2肿瘤抗原特异性CTL ,具有非常显著性差异 (P <0 0 1 ) ,接种疫苗后的小鼠能抵抗G42 2的再次攻击 (P <0 0 1 ) ,疫苗组生存期较对照组延长 (P<0 0 5)。结论 肿瘤RNA体外冲击致敏DC ,然后将之回输免疫接种至颅内荷瘤小鼠能显著地诱导机体产生抗原特异性CTL ,激活抗肿瘤T细胞 ,具有免疫保护和免疫治疗作用 。
Objective To investigate the anti tumor efficacy of dendritic cell (DC) based vaccines pulsed with tumor RNA in an mice model of intracranial G422 glioblastoma and to discuss the feasibility of this active immunotherapy strategy for gliomas.Methods Dendritic cells, the most potent antigen presenting cells in the body, were isolated from mouse bone marrow precursors stimulated in vitro with granulocyte macrophage colony stimulating factor (GM CSF) and interleukin 4(IL 4). These dendritic cells were then pulsed ex vivo with tumor RNA. 88 female mouse were treated with three weekly spaced one week apart subcutaneous injections of either PBS, unpulsed dendritic cells, G422 tumor RNA, or dendritic cells pulsed with G422 tumor RNA.7 days after the third immunization,spleens of 24 mouse were harvested for cell mediated cytotoxicity assays and other 64 mouse were challenged in the brain with G422 tumor cells. Another 64 female mouse harboring 4 day old intracranial G422 glioblastomas were treated with three weekly spaced one week apart subcutaneous injections of either PBS,unpulsed dendritic cells,G422 tumor RNA,or dendritic cells pulsed with G422 tumor RNA.These mouse were followed for survival.The mouse brains were removed and examined pathologically after they died.Survival estimates and median survival were determined using the method of Kaplan and Meier. Results Immunization using dendriric cells pulsed with tumor RNA induced G422 specific CTL responses that were statistically significant compared with mouse treated with PBS,unpulsed dendritic cells or G422 tumor RNA(P<0 01). One group of mouse were challenged with G422 tumor cells after received either PBS,unpulsed dendritic cells,G422 tumor RNA,or dendritic cells pulsed with G422 tumor RNA and significantly prolonged survival was observed in the tumor RNA pulsed dendritic cell treated group (P<0 01).The survival of intracranial tumor bearing mouse injected sudcutaneously with the syngeneic bone marrow derived dendritic cells pulsed with tumor RNA was significantly prolonged compared with that of mouse receiving PBS,unpu lsed dendriric cells,or tumor RNA(P<0 05). Conclusions Based on these results, dendtitic cells pulsed with tumor RNA derived from autologous tumors represent a promising approch to the immunotherapy of gliomas,which can specifically activate antitumor T cells and lead to significantly prolonged survival in tumor bearing animals.goustumorsrepresentapro
出处
《中华神经外科杂志》
CSCD
北大核心
2003年第2期99-102,共4页
Chinese Journal of Neurosurgery
