联合应用Ag85A和GM-CSF DNA疫苗对小鼠移植性膀胱癌BTT739细胞瘤免疫治疗的研究

摘要

目的:探讨联合应用Ag85A与GM-CSF DNA疫苗对小鼠移植性膀胱癌BTT739细胞瘤免疫治疗的效果.方法:选用小鼠膀胱癌BTT739细胞株,构建T739小鼠移植瘤模型.随机数字表法分为5组:生理盐水组、空载体组、Ag85A组、联合应用组和BCG组.荷瘤后第7天、14天和21天各肌注1次,末次注射后第7天检测各组小鼠脾脏的CD4+和CD8+ T细胞亚群数量及CD4+/CD8+比值、血清IFN-γ和肿瘤重量.结果:与生理盐水组对比,单独应用Ag85A和联合应用Ag85A与GM-CSF DNA疫苗均能够升高CD4+和CD8+ T细胞的百分比及CD4+/CD8+ 的比值,提高血清IFN-γ浓度,降低移植瘤重量,差异具有统计 学意义(P<0.05).联合应用的效果要明显优于单独应用组,差异具有统计学意义(P<0.05),但尚不及单纯应用BCG的免疫治疗效果.结论:联合应用Ag85A与GM-CSF DNA疫苗能够提高荷瘤小鼠的免疫功能,从而达到了抑制肿瘤生长的作用,其效果明显优于单独应用Ag85A DNA疫苗,二者联用具有协同增强免疫效应.%Objective:To explore the immunological therapeutic effect of combined Ag85A and GM - CSF DNA vaccine in bladder tumor - bearing mice cells.Mcthords: T739 mice with bladder cancer were constructed by injecting mice bladder cancer cell strain BTT739 subcutaneously.The mice were divided randomly into five groups :NS,pcDNA3.1, Ag85A, Ag85A + GM - CSF and BCG.DNA vaccines were injected subcutaneously the 7th day, the 14th day, and the 21th day respectively.After 7 days, the number of CD4 + and CD8 + T cell subsets was detected,the IFN -γ in mice serum was assayed.At last, the tumor was weighed.Results: Compared to NS group, Ag85A group and Ag85A + GM - CSF group can upgrade the number of CD4 + and CD8 + T cell subsets, the ratio of CD4 + /CD8 + and IFN - γ level of mice serum, and decrease the weight of tumor( P ＜ 0.05 ).The therapeutic effect of Ag85A + GM - CSF group was much better than Ag85A group( P ＜ 0.05 ), but still lower than that of BCG group.Conclusion: Ag85A and GM - CSF combined DNA vaccine can upgrade the cellular immunity to inhibit the growth of bladder cancer.Their effects are much better than Ag85A DNA vaccine alone, but still lower than BCG.