荷胃癌小鼠自杀基因治疗后宿主免疫功能观察

A Study on the Immune Response of Mice with Gastric Cancer Induced by Gene Therapy

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 study whether the suicide gene therapy can induce the immune response of the tumor bearer. Methods The tumor model was made by inoculating MFC on the back of the mice. HSV-tk gene and CD gene were injected into the tumor; mIL-2; mGM-CSF DNA were injected around the tumor; prodrugs(GVC and 5-Fc) were injected into the abdominal cavity. In the fifth week after gene treatment, the NK and LAK activities of the spleen cells from the tumor bearer were determined. In the twelfth week, the NK and CTL activities of PBL or spleen cells were tested. Results In the fifth week after gene therapy was administered, the NK and LAK activities of the spleen cells from the gene therapy experimental group were obviously higher than tumor bearer controls(P<0.01). In the twelfth week of treatment, the NK and CTL activities of PBL from experimental mice are enhanced markedly to compare with normal controls(NK, P=0.05; CTL, P<0.01). There is no difference in the NK activity of the spleen cells between experimental group and control group(P>0.05). Conclusion The suicide gene therapy can enhance the antitumor immunity ability for a rather long time.