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目的研究自杀基因疗法是否能诱导肿瘤宿主产生免疫应答。 方法将小鼠前胃癌细胞株 (MFC)接种于小鼠背部制作肿瘤模型 ,以单纯疱疹病毒胸苷激酶基因 (HSV -tk)和大肠杆菌胞嘧啶脱氧基酶基因 (CD)注射于瘤体内 ,并于瘤体周围注射mIL - 2和mGM -CSFDNA及向腹腔内注射前药 9-丙氧乌苷 (GVC)和 5 -Fc。治疗第5周取肿瘤消退小鼠的脾细胞测自然杀伤细胞 (NK)和LAK活性 ;第 12周取PBL和脾细胞测NK和细胞毒细胞(CTL)活性。 结果在TK/CD基因联合细胞因子及前药治疗后第 5周 ,实验组脾细胞NK和LAK活性均明显高于荷瘤鼠对照 (P <0 .0 1)。 12周后 ,实验组PBL的NK和CTL活性均显著高于正常对照组 (P =0 .0 5 ,P <0 .0 1) ;而脾细胞NK活性与对照组无显著差异 (P >0 .0 5 )。 结论自杀基因疗法能较长时间提高宿主抗肿瘤免疫反应。
Objective To investigate whether suicide gene therapy can induce tumor hosts to produce an immune response. Methods The mouse gastric cancer cell line (MFC) was inoculated into the back of mice to make a tumor model. The herpes simplex virus thymidine kinase gene (HSV-tk) and E. coli cytosine deoxylase gene (CD) In addition, mIL - 2 and mGM - CSF were injected into the tumor and intraperitoneal injection of prodrug 9 - propoxyalin (GVC) and 5 - Fc. At 5 weeks after treatment, NK cells and LAK activity were measured in spleen cells from mice with tumor regression; NK and cytotoxic (CTL) activities of PBL and spleen cells were measured at the 12th week. Results The activity of NK and LAK in spleen cells of experimental group was obviously higher than that of tumor-bearing mice (P <0.01) at the 5th week after TK / CD gene combined with cytokines and prodrugs. After 12 weeks, NK and CTL activities of PBL in the experimental group were significantly higher than those in the normal control group (P = 0.05, P <0.01); while NK activity in the spleen cells was not significantly different from that in the control group .0 5). Conclusion Suicide gene therapy can improve host anti-tumor immune response for a long time.