突变k-ras基因修饰的树突状细胞疫苗的抗肿瘤作用

In vivo anti-tumor response induced by dendritic cell vaccine modified by mutant k-ras genes

目的探讨腺病毒介导的突变kras基因修饰的树突状细胞疫苗在体内的抗肿瘤作用。方法将突变kras基因修饰的DC经腹腔注射免疫小鼠(5×105/只),1次/周,共2次,随后将肿瘤细胞接种于皮下,观察DC能否诱发机体的免疫保护。结果突变kras基因修饰的DC疫苗组Lewis肺癌(3LL)移植瘤生长明显延缓,肿瘤体积显著低于空载体组、DC组和对照组(P<0.05),而抑瘤率显著高于空载体组、DC组和对照组(P<0.05)。突变kras基因修饰的DC疫苗组Lewis肺癌(3LL)移植瘤肺转移率(2/10,20%)显著低于空载体组(6/10,60%)、DC组(6/10,60%)和对照组(8/10,80%,P<0.05);肺部转移灶数目亦显著少于空载体组、DC组和对照组(P<0.05)。结论突变kras基因修饰的DC疫苗能有效诱导机体产生特异的抗肿瘤免疫反应,抑制Lewis肺癌生长和远处转移。

Objective To study in vivo specific anti-tumor immune response induced by dendritic cell （DC） vaccine modified by mutant k-ras genes. Methods The DCs modified with mutant k-ras genes （5 × 10^5）, once a week for 2 weeks, were injected intraperitoneally into abdominal cavity to immunize the mice. The tumor cells were subcutaneously inoculated to observe whether the DCs could induce the immune protection. Results The tumorigenesis of transplanted tumor with Lewis lung cancer cells in the mice vaccined with mutant k-ras-modified DCs was significantly suppressed. The volume and weight of transplant tumor in the k-ras-DC group were remarkably decreased as compared with those in control, vector and non-modified DC groups （P〈 0.05）. The inhibitory rate of tumor growth in the k-ras-DC group was significantly higher than that in the control, vector and non-modified DC groups （P〈 0.05）. The lung metastasis rate of transplanted tumor in the mice （20 % ） vaccined with mutant k-ras gene-mod- ified DCs was significantly lower than in the control （80%）, vector （60%） and non-modified DC groups （60 %, P 〈 0.05）. The lung metastastic loci in k-ras-DC group were also significantly less than those in the control, vector and non-modified DC groups （ P 〈 0.05）. Conclusion Specific antitumor immune response could be induced effectively by CD vaccine modified with mutant k-ras gene. In addition, DC vaccine modified with mutant k-ras gene could remarkably suppress the growth and distant metastasis of Lewis lung cancer.