【摘要】 目的探讨树突状细胞(DCs)疫苗在人源化裸鼠体内的抗胃癌免疫保护作用。方法制备DCRNA疫苗;建立人源化裸鼠模型;15只人源化裸鼠随机分为DCRNA组、DCs组和PBS组,每组5只,分别用DCRNA、DCs和PBS皮下免疫注射2次,间隔1周,末次免疫后3天皮下接种胃癌细胞。各组裸鼠外周血人源性CD4(T细胞和CD8(T细胞的检测和观察GVHD反应。观察裸鼠瘤体积和瘤重。检测细胞因子IL-12和IFN-γ水平。结果各组HuPBTL-裸鼠外周血中均检测到人源性CD4(T细胞和CD8(T细胞,无GVHD反应。DCRNA组瘤体积明显小于DCs组和PBS组(P<0.05);DCRNA组瘤重明显小于DCs组和PBS组(P=0.0452、P=0.0004),但DCs组和PBS组差异无统计学意义(P=0.0618);DCRNA组抑瘤率(53.7%)显著高于DCs组(25.1%)(P<0.05)。DCRNA组IL-12和IFN-γ水平明显高于DCs组和PBS组(P<0.05、P<0.01)。结论HuPBTL腹腔注射,可成功构建裸鼠人细胞免疫功能;DC疫苗在人源化裸鼠体内能诱导产生较强的抗胃癌免疫保护作用。更多还原

【Abstract】 Objective To explore antitumor protective immunity induced by dendritic cells based vaccine in humanised nude mice model.Methods Immature DCs generated from peripheral blood mononuclear cells were transfected with gastric carcinoma total RNA in vitro.A humanized nude mice model was established by intraperitoneal(i.p.)injection of human peripheral blood T-lymphocytes(HuPBTL).The mice were randomly divided into DCRNA group,DCs group and PBS group of 5 mice each.The mice were immunized s.c.with DCRNA or DCs and PBS,respectively,twice,at weekly intervals.Three days after the last immunization mice were challenged s.c.with BGC-823 cells.The CD4+ and CD8+ T cell subpopulations of human T-lymphocytes from peripheral blood of humanised nude mice were detected by flow cytometry and graft versus host disease(GVHD)were observed.Tumor growth,tumor volume,tumor weight and tumor inhibition rate were observed.Production of cytokine IL-12 and IFN-γwere detected by ELISA kit.Results The CD4+ and CD8+ T cells subpopulations of human T-lymphocytes from peripheral blood of humanised nude mice were found in each group.GVHD was not occurrence in each group.Overall tumor volume in DCRNA group mice was significantly lower than those of DCs group and PBS group(P<0.05).Tumor weight in DCRNA group was significantly lighter than those of DCs group and PBS group(P=0.0452,P=0.0004),but this difference was not statistically significant between DCs group and PBS group(P=0.0618).Inhibition tumor rate for DCRNA group(53.7%)was higher than that for DCs group(25.1%)(P<0.05).Production of cytokine IL-12 and IFN-γin DCRNA group were significantly increased relatived to DCs group and PBS group(P<0.05,P<0.01).Conclusion A humanised nude mouse model was successfully established by i.p.injection of HuPBTL.DCs based vaccine is capable of inducing enhanced antitumor protective immunity in vivo.更多还原