MUC1基因疫苗对膀胱肿瘤抑制的免疫学实验研究  

The immunological investigation for anti-tumor roles of MUC1 vaccine in the bladder cancer

作　　者：罗刚[1] 周四维[2] 李志坚[1] 黎卫[1] 周华扩[1] 黄红星[1] 高新[3] 

机构地区：[1]中山大学附属中山医院泌尿外科,中山528403 [2]华中科技大学同济医学院附属同济医院泌尿外科,武汉430030 [3]中山大学附属第三医院泌尿外科,广州510630

出　　处：《中国免疫学杂志》2008年第8期694-697,共4页Chinese Journal of Immunology

基　　金：国家自然科学基金资助项目(30271300)

摘　　要：目的:研究人粘蛋白MUC1基因DNA疫苗诱导小鼠细胞毒性T细胞(CTL)及体液免疫应答的作用,为膀胱癌的疫苗治疗提供实验资料。方法:接种pcDNA3.1(+)-MUC1质粒,通过ELISA法检测小鼠血清MUC1抗体生成和脾细胞产生IL-2和IFN-γ的量,通过LDH释放法测定CTL对BIU-87细胞的杀伤活性。结果:接种pcDNA3.1(+)-MUC1疫苗后,小鼠血清中抗MUC1抗体水平明显升高,与对照组相比有显著性差异(P<0.01)。脾细胞产生的IL-2和IFN-γ水平较对照组高(P<0.01)。在效靶比为100∶1、50∶1、25∶1、12.5∶1时,MUC1基因疫苗免疫组小鼠CTL对BIU-87杀伤率(分别为58.4%、47.2%、35.7%、27.4%),较空载体pcDNA3.1(+)组小鼠和灭菌生理盐水组小鼠(分别为11%、19.2%、9.5%、14%和16.5%、11.9%、8.6%、10.3%)均明显升高,且有显著性差异(P<0.01)。结论:MUC1基因DNA疫苗能够诱导小鼠产生抗MUC1特异性抗体,诱导产生杀伤表达MUC1细胞的CTL,为MUC1基因疫苗用于膀胱肿瘤生物治疗提供了一定的实验依据。Objective： To study the effects of a DNA vaccine containing human mucin gene for inducing cytotoxic T lymphecytes （CIL） and humoral immune responses, whereby to provide the basic experimental data for clinic application of the regimen in human bladder cancer. Methods： The pcDNA3.1 （ ＋ ）-MUC1 plasmid was used to immunize male BALB/c mice. Subsequently, the level of anti-MUC1 antibody, IL-2 and IFN-T in sere of the mice were examined by ELISA. The cytotoxicity of CTLs from the mice targeting to BIU-87 cells was examined by LDH release assay. Results： The levels of antibodies against MUC1, of IL-2 and IFN-γ in sera of the mice were increased after immunization with the plasmid as compared with those of the control groups.At the ratios of effector cells to target cells of 100：1,50：1,25：1 and 12.5：1 ,specific cytotoxicity of the spleen cells in pcDNA3.1（ ＋ ）-MUC1 groups （58.4%,47.2%,35.7%,27.4%） was higher than in the control groups （ 11%, 19.2% ,9.5%, 14% ; 16.5%, 11.9% ,8.6%, 10.3 % ,respectively） （ P 〈 0.01）. Conclusion： The constructed DNA vaccines can induce production of antibody against MUC1. CrLs toward the target cells expressing MUC1 ,the human bladder cancer,can be trigered by immunization with the DNA vaccine. The study supports application of MUC1 vaccinination in the therapy of human bladder cancer.

关 键 词：MUC1 DNA疫苗 细胞毒性T细胞 膀胱肿瘤 

分 类 号：R737.14[医药卫生—肿瘤]