CD基因联合IL-18基因对小鼠胰腺癌的疗效及其免疫机制

目的：研究自杀基因与IL-18基因联合治疗胰腺癌的作用及其免疫机制。方法：构建小鼠IL-18基因和CD基因逆转录病毒质粒pVITR02-CD-IL-18。小鼠皮下接种小鼠胰腺癌细胞TD2，肿瘤局部注射重组表达的pVTTPO2-CD-Ⅱ，18逆转录病毒，然后连续10d给予5-氟胞嘧啶(5-Fc)300mg／kg进行治疗，分别观察肿瘤的生长情况。结果：联合IL-18基N治疗后，肿瘤体积显著缩小，小鼠存活期明显长于对照组，肿瘤瘤体内CD8^ 细胞浸润增加；肿瘤细胞表达H-2D^b和B7-1分子明显增加。结论：联合应用自杀基因和IL-18基因转移可以直接杀伤肿瘤细胞，它既有效地减少了肿瘤负荷，又充分调动了机体的抗肿瘤免疫，提高疗效。

Therapeutic effect of combined treatment with CD suicide gene and IL-18 gene on murine pancreatic cancer and research on its immunological mechanism

Objective:To study the role and immunological mechnisms of combined treatment with CD suicide gene and IL-18 gene on the pancreatic cancer.Methods:pVITRO2-CD-IL-18 was transfected by injecting the virus supernatant into the tumors and 5-Fc were used. The growth and changes of the tumor were observed.Results:The growth of transduced cells xenografts could be totally regressed by 5-FC. Combination of CD gene with IL-18 gene could enhance the killing effect and lessened the tumor mass. The results demonstrated that significant growth inhibition of established tumors and prolongation of survival period were observed in tumor-bearing mice after CD and IL-18 combined therapy when compared with mice treated with CD,IL-18,P<0.05. The expression of MHC-I and B7-1 molecules on freshly isolated tumor cells after combined therapy increased greatly,and more CD8 + T cells infiltrated into the tumor mass when measured with FACS.Conclusion:The results suggest that combined therapy with suicide gene and CD gene transfer can directly eradicate established tumors and efficiently induce the antitumor immunity of the mice.