【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。更多还原

【Abstract】 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 in- vestigated.It was found that the tumor vaccine modified by IL-18 gene could definitely prolong the survival time of tumor-bear- ing 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 pro- tective immunity as well.It was also demonstrated that inoculation of mice with this vaccine induced enhanced activities of cyto- toxic T lymphocytes(CTL)and NK cells remarkably.Although the level of IFN-γproduction was also elevated under this con- dition,yet the difference compared with that of controls was not significant,indicating that IFN-γmay play a minor role in the immune responses induced by this tumor vaccine.更多还原