TIM2转基因细胞瘤苗对小鼠作用的初步研究  

Tumor-cell-based vaccine modified by TIM2 gene transfer in mice

作　　者：马玲娣[1] 文世宏[1] 张彦[2] 何於娟[2] 刘小珊[3] 康格非[2] 蒋纪恺[3] 

机构地区：[1]南京医科大学附属常州第二人民医院中心实验室,常州213003 [2]重庆医科大学检验系临床生化教研室,重庆400016 [3]广东汕头大学医学院分子生物学中心,广东汕头515031

出　　处：《免疫学杂志》2008年第1期16-18,22,共4页Immunological Journal

基　　金：国家自然科学基金资助(30171150)

摘　　要：目的观察小鼠TIM2转基因H22肝癌细胞瘤苗在小鼠体内的成瘤作用,初步研究其免疫原性。方法构建TIM2基因真核表达载体pIRES2-EGFP-TIM2,脂质体法转染H22细胞,制备得到TIM2基因修饰的H22细胞瘤苗,建立小鼠肝癌移植瘤模型,观察其在小鼠体内的成瘤作用。结果成功得到TIM2基因修饰的H22细胞瘤苗,免疫接种小鼠后,可明显抑制小鼠体内肿瘤的发生和发展;给予H22-TIM2接种的小鼠CD4亚群、CD4/CD8比值显著高于H22-EGFP细胞接种组、荷瘤对照组和正常对照组。结论TIM2基因修饰H22细胞后,可显著降低H22细胞的体内成瘤性,抑制小鼠肿瘤生长,同时。在体内具有一定的免疫原性,为进一步探讨TIM2在肿瘤生物治疗中的作用提供了初步的实验依据。Objective To investigate the effect of H22 hepatocareinoma cell-based vaccine modified by ex vivo TIM2 gene transfer in mice, and explore its immunogenic profile in vivo. Methods A combinant eukaryotic expression vector contained TIM2 gene was constructed and transfection into H22 cells by lipofectamin. The H22-TIM2 cell line expressed ex-vivo TIM2 gene was obtained by stable electing essay in vitro. The TIM2 mRNA expression was detected by RT-PCR; the expression of TIM2 protein was indicated by expression of EGFP protein, which was determined using fluorescent microscope. Then the Balb/c mice were vaccinated with H22-TIM2 cells to establish the tumor-bearing model. The H22-EGFP cells transfected with pIRES2-EGFP vector and H22 cells were used as the experimental control. The oncogenicity of the TIM2 gene-modified H22 cells and its effects on tumor growth were observed in vivo. Results The co-expression of EGFP and TIM2 genes was detected after TIM2 gene transfection into H22 cells. The growth of tumor was significantly inhibited in mice vaccinated with H22-TIM2 cell line. The populations of CD4-positive lymphecytes and the ratio of CD4-positive to CD8-positive lymphecytes in spleen of mice vaccinated of H22-TIM2 cells were obviously higher than those of the other groups. Conclusion The tumorigenesis of H22 cells is markedly impaired after transfection of TIM2 gene. The H22 cell vaccine modified with TIM2 gene presents immunogenicity in some part and suppresses the growth of tumor in vivo. The results provide a preliminary study for biotherapy of tumor with TIM2 gene.

关 键 词：TIM12基因 肿瘤 生物治疗 瘤苗 

分 类 号：R392[医药卫生—免疫学]