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目的:观察自杀基因与细胞因子基因联合转移的抗肿瘤作用与免疫机制。方法:将表达大肠杆菌胞嘧啶脱胺酶(CD)的重组腺病毒(AdCD)及表达小鼠粒巨噬细胞集落刺激因子(GMCSF)基因的重组腺病毒(AdGMCSF)直接进行体内注射,合并应用5氟胞嘧啶(5FC)对红白血病皮下荷瘤小鼠模型进行治疗。结果: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<0.05);免疫功能检测表明,联合基因治疗组小鼠CTL杀伤活性明显高于单用AdCD/5FC、AdGMCSF、对照病毒AdLacZ/5FC或PBS治疗组;病理分析显示,联合基因治疗组肿瘤细胞发生明显坏死,瘤内及瘤周有大量的炎性细胞浸润。结论:应用自杀基因与细胞因子基因联合转染可更有效地抑制荷瘤小鼠肿瘤的生长,且可诱导抗肿瘤免疫应答
Objective: To observe the anti-tumor effect and immune mechanism of combined transfer of suicide gene and cytokine gene. Methods: Recombinant adenovirus (AdCD) expressing Escherichia coli cytosine deaminase (CD) and recombinant adenovirus (GMCSF) expressing mouse granulocyte macrophage colony stimulating factor (AdGM) CSF) was directly injected in vivo and 5-fluorocytosine (5FC) was combined to treat a subcutaneous tumor bearing mouse model of erythroleukemia. RESULTS: Combined gene therapy significantly inhibited the growth of subcutaneous tumors in tumor-bearing mice and significantly prolonged their survival time (P<0.05). The immune function test showed that the killing activity of CTL in mice combined with gene therapy was significantly higher than that of mice alone. AdCD/5FC, AdGMCSF, control virus AdLacZ/5FC or PBS treatment group; pathological analysis showed that necrosis of tumor cells occurred in the combined gene therapy group, and there was a large number of inflammatory cell infiltrations in and around the tumor. . Conclusion: The combination of suicide gene and cytokine gene transfection can effectively inhibit tumor growth in tumor-bearing mice and induce anti-tumor immune response.