RNA致敏树突状细胞治疗胶质瘤的实验研究

目的:肿瘤RNA致敏树突状细胞(DC)治疗颅内荷瘤小鼠,观察DC疫苗对脑胶质瘤的治疗作用,探讨免疫反应的机理,为DC疫苗的临床应用提供实验基础。方法:用G422胶质母细胞瘤RNA冲击致敏DC制成DC疫苗,检测DC疫苗的CTL活性,瘤内和皮下两种途径注射荷瘤小鼠以进行免疫治疗,观察小鼠生存期,并与PBS、单纯DC组进行比较,同时检测血清IFN-γ、IL-2、IL-10、IL-4等细胞因子,并行病理检查。结果:DC疫苗的CTL活性明显高于对照组(P<0.01)。两种途径注射DC疫苗,治疗组小鼠生存时间均明显延长(P<0.01),血清IFN-γ显著升高(P<0.01),IL-10明显下降(P<0.05),病理提示肿瘤出现坏死。两种注射途径间以上指标无明显差异。结论:肿瘤RNA冲击致敏DC注射荷瘤小鼠具有明显的免疫治疗作用,能显著延长动物生存期,并能诱导特异性抗肿瘤细胞免疫反应,其机理主要是Th1细胞介导的细胞免疫反应,且免疫反应的程度与注射途径无关。

Dendritic cells pulsed with glioma RNA induce immunity against intracranial gliomas

OBJECTIVE: To investigate the anti-tumor effect of dendritic cells (DC) pulsed with G422 glioblastomas RNA in mice bearing intracranially G422 glioblastomas. METHODS: DCs were pulsed in vitro with glioblastomas G422 cell RNA. The tumor-bearing mice were injected intratumorally or subcutaneously with pulsed DCs, PBS, non-pulsed DCs. The survival duration of mice was recorded. Serum levels of cytokine IFN-gamma, IL-2, IL-10, IL-4 were detected. Pathological examination was performed. RESULTS: The survival duration of mice with DC-based vaccine increased significantly(P<0.01). The serum IFN-gamma level was increased (P<0.01) and IL-10 level was decreased (P<0.05) after treatment. Pathological examination showed necrotic tumor in the treatment mice. CONCLUSION: DC vaccination can significantly increase survival duration of mice with intratumoral or subcutaneous administration of vaccines.