小鼠IL-18基因修饰瘤苗的抗白血病作用研究  

The anti-leukemia effect of tumor vaccine modified by IL-18 gene in mice

作　　者：徐玢[1] 马小彤[1] 董成亚[1] 石洋[1] 林永敏[1] 吴克复[1] 

机构地区：[1]中国医学科学院中国协和医科大学血液学研究所血液病医院实验血液学国家重点实验室,天津300020

出　　处：《现代免疫学》2007年第4期274-278,共5页Current Immunology

基　　金：国家自然科学基金(30471964);天津市自然科学基金(05YFJMJC02200)

摘　　要：我们在前期工作中成功制备了IL-18基因修饰的白血病疫苗,为了探讨IL-18基因修饰瘤苗的体内抗白血病作用,实验采用L1210小鼠淋巴细胞白血病模型,在小鼠体内接种IL-18基因修饰瘤苗,观察瘤苗对L1210细胞致瘤性的影响及免疫保护作用,并进一步对其抗白血病作用机制进行了探索。结果显示,IL-18基因修饰瘤苗能够明显延长荷瘤小鼠存活时间,大部分小鼠达到长期生存,且长生存小鼠用野生型L1210细胞二次攻击后大多数仍能长期生存,表明IL-18基因修饰瘤苗有显著的抗白血病作用,并可诱导小鼠产生免疫记忆和免疫保护。机制探讨发现,接种IL-18基因修饰瘤苗后,小鼠脾脏淋巴细胞对L1210肿瘤细胞的CTL及NK细胞杀伤活性明显高于对照组(P<0.05),提示IL-18基因修饰瘤苗能够显著增强抗肿瘤CTL和NK细胞反应。接种瘤苗可使小鼠IFN-γ水平升高,但与对照相比无统计学意义,提示IFN-γ可能在IL-18基因修饰瘤苗诱导的抗肿瘤免疫应答中作用不大。In our previous work,we have successfully constructed the tumor vaccine modified by IL-18 gene. In order to explore the in vitro anti-leukemia effect induced, the murine lymphocytic leukemia L1210 model was inoculated with this tomor vaccine, and the effect on the leukemogenicity,protective immunity and anti-leukemia mechanism induced by this tumor vaccine were investigated. It was found that the tumor vaccine modified by IL-18 gene could definitely prolong the survival time of tumor-bearing mice,in which most mice lived for a long time and majority of them could sustain the second challenge with parental L1210 cells in a longer survival time,indicating that this kind of tumor vaccine could elicit potent anti-tumor immunity and induce protective immunity as well. It was also demonstrated that inoculation of mice with this vaccine induced enhanced activities of cytotoxic T lymphocytes （CTL） and NK cells remarkably. Although the level of IFN-γ production was also elevated under this condition,yet the difference compared with that of controls was not significant,indicating that IFN-γ may play a minor role in the immune responses induced by this tumor vaccine.

关 键 词：白细胞介素18 L1210白血病 肿瘤疫苗 

分 类 号：R392.11[医药卫生—免疫学]