不同细胞因子基因转导对小鼠B16细胞体内生长及免疫原性的影响

于晓盽　唐佩弦　张明伟　黄　英　彭善云　侯春梅　刘元林　毛　宁

　　中国图书分类号　R73-3
　　摘　要　目的：通过比较不同细胞因子基因转导对肿瘤细胞体内生长及对机体免疫活性的影响，探讨其可能的作用机制及因子间的协同效果。方法：采用逆转录病毒介导的方法将IL-6/IL-2融合基因及IL-6、IL-2单基因分别导入小鼠B16黑色素瘤细胞中，检测基因修饰瘤细胞体内成瘤及对机体LAK、CTL活性的诱导。结果：三种基因修饰的肿瘤细胞均可表现出体内生长抑制及免疫原性增强，但融合基因转导细胞的改变，较单一基因修饰细胞更为明显。结论：融合基因转导可较单一基因转导具有更好的肿瘤细胞修饰效果。
　　关键词　基因转导　肿瘤细胞　免疫调控

Effect of various cytokine gene transduction on B16 cell growth in vivo and immunogenicity

YU Xiao-Dan,TANG Pei-Xian,ZHANG Ming-Wei et al.
Institute of Basic Medical Sciences Academy of Military Medical Science,Beijing 100850

　　Abstract　Objective:To investigate the modulation mechanism of various cytokine gene-transfer on tumor cell biological characteristics and the synergetic effect between cytokines,studied the effect of single IL-2,IL-6 gene or IL-6/IL-2 fusion gene transduction on tumor cell growth in vivo and immunogenicity.Methods:Constructed three retroviral vectors contained hIL-6,hIL-2 single gene or hIL-6-/IL-2 fused gene.The vectors were transferred into B16 melanoma cell line respectively and the influence of gene transfer on tumorigenicity and the LAK and CTL cytotoxic activities of vaccinated mice splenocytes were examined.Results:B16 cells modified by various gene showed decreased tumorigenicity and enhanced LAK,CTL cytotoxicity.The changes of fusion gene-transfectant is more obvious than that of single gene-transfectants.Conclusion:The efficiency of tumor cell modification induced by various cytokine gene-transfer is different,as the synergetic effect ,the effect induced by IL-6/IL-2 fusion gene-transfer is superior to that of the IL-6 and IL-2 gene alone.
　　Key words　Gene transfer　Tumor cell　Immuno-modulation

　　将经细胞因子基因修饰后的肿瘤细胞作为瘤苗用于肿瘤的免疫治疗，正成为肿瘤生物治疗研究的重要组成部分。为探讨不同的细胞因子基因转导对肿瘤细胞影响的差异及两种细胞因子基因转导对于肿瘤细胞修饰的协同作用，构建了含人IL-6、IL-2单基因及IL-6/IL-2融合基因的逆病毒载体。将三种基因分别导入小鼠黑色素细胞瘤B16细胞中，对不同基因转导细胞对肿瘤细胞的修饰及对机体免疫活性的刺激等方面进行了深入的实验研究。

1　材料与方法
1.1　实验试剂　所用试剂分别购自Promega及华美

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