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单用自杀基因疗法或单用细胞因子基因疗法抗肿瘤效果不理想,本研究中我们观察了大肠杆菌胞嘧啶脱胺酶(CD)基因与白细胞介素2(IL-2)基因联合转移对荷瘤小鼠的治疗效果及其对抗肿瘤免疫的诱导作用。复制荷瘤小鼠模型后在荷瘤部位注射表达CD基因的重组腺病毒(AdCD)及表达小鼠IL-2基因的重组腺病毒(AdIL2),并连续10天、每天1次腹腔注射5氟胞嘧啶(5FC)对荷瘤小鼠进行治疗。结果表明,AdCD/5FC/AdIL2联合基因治疗能显著抑制荷瘤小鼠皮下肿瘤的生长,并明显延长其生存期(P<0.01)。联合基因治疗组小鼠肿瘤细胞发生明显的坏死,瘤内及瘤周有大量的炎性细胞浸润,瘤内CD4~+和CD8~+T细胞明显增加,脾细胞NK和CIL杀伤活性明显高于单用AdCD/5FC、对照病毒AdLacZ/5FC或PBS组。实验结果表明,联合应用自杀基因与细胞因子基因治疗可更有效诱导机体的抗肿瘤免疫反应,从而更显著地抑制荷瘤小鼠肿瘤的生长。
The anti-tumor effect of suicide gene therapy alone or cytokine gene therapy alone is not ideal. In this study, we observed the combined transfer of cytosine deaminase (CD) gene and interleukin 2 (IL-2) gene to E. coli. Therapeutic effects of tumor mice and their induction of antitumor immunity. After replication of the tumor-bearing mouse model, the recombinant adenovirus expressing the CD gene (AdCD) and the recombinant adenovirus expressing the mouse IL-2 gene (AdIL2) were injected into the tumor-bearing site and injected intraperitoneally once daily for 10 days. Cytosine (5FC) was used to treat tumor-bearing mice. The results showed that AdCD/5FC/AdIL2 combined gene therapy significantly inhibited the growth of subcutaneous tumors in tumor-bearing mice and significantly prolonged their survival (P<0.01). Significant necrosis of tumor cells was observed in the mice of the combined gene therapy group. A large number of inflammatory cells infiltrated in and around the tumors. The number of CD4+ and CD8+ T cells in the tumors increased significantly. The killing activity of NK and CIL in spleen cells was significantly higher than that in the tumor cells. AdCD/5FC alone, control virus AdLacZ/5FC or PBS group. The experimental results show that the combined application of suicide gene and cytokine gene therapy can more effectively induce the body’s anti-tumor immune response, thereby more significantly inhibiting tumor growth in tumor-bearing mice.