目的:为观察携带小鼠白细胞介素12(mIL-12)逆转录病毒包装细胞株在肝癌局部注射后,对体内肝癌治疗效果.方法:构建携带mIL-12的逆转录病毒载体,将该载体转染包装细胞系PA317,应用该包装细胞对实验性原位肝癌大鼠分别在不同时间进行治疗,观察其抗肿瘤作用,免疫功能变化,病理及毒性反应.结果:携带mIL-12逆转录病毒包装细胞(PA317-mIL-12)在原位肝癌局部注射后能明显抑制肝癌细胞生长,其早期治疗可使大鼠长期生存,中晚期治疗,大鼠虽然不能长期生存,但较空白对照组及携带空载体对照组的生存期明显延长,(P<0.01).其治疗组NK细胞及T细胞明显增加,其早期治疗效果优于中期治疗,另外,本研究对肝癌局部进行IL-12基因转染,可使另一叶肝癌消退,这表明IL-12可通过激活机体免疫细胞,杀灭未转染的肿瘤细胞,这对于临床应用IL-12基因治疗非常重要.同时,生存期超过2个月大鼠,再次接种相当数量的肝癌细胞,该大鼠不能再次形成肝癌.结论:肝癌局部注射IL-12基因能激发机体抗肿瘤免疫反应.

Objective: To investigate the antitumor effects and the possible mechanisms of tumor antigen peptide-pulsed, IL-2 gene-modified dendritic cells (DCs) in combination with low-dose cyclophosphamide (Cy). Methods: Mutl is a MHC class I -restricted tumor antigen peptide of 3LL Lewis lung carcinoma. The mice bearing metastatic lung carcinoma were treated by vaccination with DCs transfected with IL-2 gene and pulsed with Mutl, then the survival period of mice were observed. The phenotypes of splenocytes were detected by FACS and the cytotoxicity of CTL and NK were assayed by 4h-51Cr release assay. Results: The combind treatment could inhibit pulmonary metastasis of tumor most significantly and increase the proportion of the CD8 T cells, NK1.1 cells in spleen mononuclear cells. The highest CTL cytotoxicity could be induced. Conclusion: Tumor antigen peptide-pulsed,IL-2 gene-modified DCs combined with low-dose Cy could induce antitumor immune response most potently and then inhibit tumor pulmonary metastasis most significantly.

R730.5

国家自然科学基金重点项目(批准号39730440);上海市现代生物与新药产业发展基金(批准号984319119);国家自然科学基金(批准号39870760)资助项目