IL-12基因转导EL-4细胞对C57BL/6小鼠的肿瘤疫苗作用

Effect of Tumor Vaccine of EL-4 Cell Transduced with IL-12 Gene in C57BL/6 Mice

应用逆转录病毒构建了IL 12表达载体 ,以研究IL 12基因修饰的肿瘤细胞的肿瘤疫苗作用 ,将其转染EL 4胸腺瘤细胞并研究了该基因导入细胞的抗肿瘤免疫效果。当接种了EL 4 /IL 12转染细胞后 ,在C5 7BL/ 6同系鼠中其基因导入细胞的致瘤性比EL 4 /Wt和EL 4 /Neo组明显减少 (P <0 .0 1) ,在EL 4 /IL 12被排斥后 ,体内试验中实验动物诱发了抗EL 4 /Wt的系统性、保护性免疫 ,51Cr释放测定中 ,获得一个较强的抗EL 4 /Wt和一个较弱的抗同系Lewis肿瘤细胞的CTL活性 ,体内淋巴细胞消除分析的结果提示减少的致瘤性主要依赖于CD4 +,CD8+和NK细胞。这一研究结果提示应用IL 12进行血液肿瘤的治疗是有效的 ,在未来人类癌症的治疗中IL

In order to study the vaccine potency of gene modified tumor cells, IL 12 express vector was constructed by using retrovirus. The vector was transfected into EL 4 thymic lymphoma cells and the effect of transfectant on anti tumor immunity was investigated. The tumorigenicity of EL 4/IL 12 transfectant in syngeneic C57BL/6 mice was decreased significantly after implanted with EL 4/IL 12 transfectant compared with EL 4/Wt or EL 4/Neo groups (P<0.001). The systemic protective immunity was induced against the challenge with EL 4/Wt (in 8/10 mice) after the rejection of EL 4/IL 12 in vivo experiment, a stronger CTL activity against EL 4/Wt cells and a weak killer activity against syngeneic Lewis lung carcinoma (LLC) cells were obtained in 51 Cr release assay. In vivo depletion analysis suggested that the decreased tumorigenicity mainly depended on CD4 +, CD8 + and NK cells. Therapeutic vaccines with EL 4/IL 12 cells could retard the growth of established EL 4/Wt tumors significantly compared with those of EL 4/Neo (P<0.005). These studies suggested that immunotherapy and gene therapy using IL 12 is effective in hematopoietic malignancy and IL 12 has prospects of application in human cancer treatment in the near future.