多基因修饰的胶质瘤细胞接种后机体免疫功能的变化

Immunity of Tumor-bearing Mice Inoculated By IL-2 Gene And B7-1 Gene Co-transfected Glioblastoma Cells

目的研究如何提高胶质瘤细胞的免疫原性,探讨胶质瘤免疫治疗的新途径。方法用重组腺病毒作载体,将共刺激分子B7-1基因和具有多重免疫功能的IL-2基因转入G422小鼠胶质母细胞瘤细胞中,取1×105个细胞(体积0.1ml),在小鼠皮下接种,分野生型对照组、lacZ组、IL-2组、B7-1组和B7-1+IL-2组。接种后不同时间测量肿瘤大小。两周后检测荷瘤小鼠脾细胞的NK、LAK和CTL的活性及细胞因子的分泌。结果B7-1+IL-2组肿瘤生长明显受抑制(P<0.05)。B7-1组的NK、LAK、CTL的杀伤活性及脾细胞分泌细胞因子的水平都很低,与对照组相差不显著。IL-2组的CTL的杀伤活性较高,与对照组相差显著(P<0.05),而NK和LAK活性及细胞因子水平与对照组相差不显著。B7-1+IL-2组的NK、LAK、CTL和脾细胞分泌细胞因子的活性与对照组相比,相差都非常显著(P<0.01)。结论单纯B7-1基因转染G422细胞不能增强其免疫原性;IL-2基因转染后,对机体的免疫反应有一定的增强作用,但效果不够理想;B7-1基因和IL-2基因联合转染G422细胞则可以明显增强其免疫原性,并有效激活荷瘤小鼠的特异性抗肿瘤免疫反应。

Objective To explore a new way of glioblastoma immunotherapy. Methods G422 murine glioblastoma cells were divided into 5 groups and gene transfected with adenovirus vector: wide type, lacZ gene, IL-2 gene, B7-1gene, and IL-2 gene plus B7-1 gene. 1×105 gene- transfected G422 glioblastoma cells were inoculated subcutaneously in the mice. The tumor growth were observed, and the cytotoxicity of NK, LAK and CTL induced and cytokines excreted by splenocytes were tested 2 weeks after the inoculation. Results After the subcutanous inoculation of IL-2 gene and B7-1 gene co-transfected G422 cells, the tumor growth was decreased (P<0.05). The cytotoxicity of NK, LAK and CTL and cytokines excreted by splenocytes were significantly increased as compared the control group (P<0.01). Conclusion The immunogenicity of IL-2 gene and B7-1 gene co-transfected G422 glioblastoma cells is increased, and the antitumor immune response can be significantly induced by the subcutanous inculation of them in the mice.[