在CT26肿瘤模型中，单纯疱疹病毒胸苷激酶自杀基因疗法与γ-干扰素/粒细胞-巨噬细胞集落刺激因子细胞因子基因疗法联合使用可增强抗肿瘤效果。

Increased anti-tumor effect by a combination of HSV thymidine kinase suicide gene therapy and interferon-gamma/GM-CSF cytokine gene therapy in CT26 tumor model.

作者信息

Yang Sung Hyun, Oh Tae Keun, Kim Seung Taik

机构信息

Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.

出版信息

J Korean Med Sci. 2005 Dec;20(6):932-7. doi: 10.3346/jkms.2005.20.6.932.

The potential therapeutic benefit of introducing IFN-gamma and GM-CSF genes in combination with the HSVtk suicide gene into subcutaneously implanted CT26 tumor cells was compared with that from each treatment alone. Cells, unmodified or retrovirally transduced with HSVtk or IFN-gamma/GM-CSF genes, were inoculated subcutaneously into syngeneic BALB/c mice in various combinations. HSVtk gene, with intraperitoneal ganciclovir treatment, reduced tumor volume by 81% at locally inoculated tumor sites (p < 0.01) and by 25% at distantly inoculated tumor sites (p = 0.052). IFN-gamma/GM-CSF genes showed a 56% tumor volume reduction at local tumor sites (p < 0.01) and 15% volume reduction at remote tumor sites, although this was not statistically significant. The combination of HSVtk (with GCV) and IFN-gamma/GM-CSF genes showed an 81% volume reduction at local tumor sites (p < 0.01) and a 43% volume reduction at remote tumor sites (p < 0.01). Thus, the combination of HSVtk and IFN-gamma/GM-CSF gene therapy produced greater therapeutic efficacy than either treatment alone.

将干扰素-γ（IFN-γ）基因和粒细胞-巨噬细胞集落刺激因子（GM-CSF）基因与单纯疱疹病毒胸苷激酶（HSVtk）自杀基因联合导入皮下植入的CT26肿瘤细胞的潜在治疗益处，与单独使用每种治疗方法的益处进行了比较。将未修饰的细胞或用HSVtk或IFN-γ/GM-CSF基因进行逆转录病毒转导的细胞，以各种组合皮下接种到同基因的BALB/c小鼠体内。HSVtk基因联合腹腔注射更昔洛韦治疗，在局部接种肿瘤部位使肿瘤体积减少81%（p<0.01），在远处接种肿瘤部位使肿瘤体积减少25%（p = 0.052）。IFN-γ/GM-CSF基因在局部肿瘤部位使肿瘤体积减少56%（p<0.01），在远处肿瘤部位使肿瘤体积减少15%，尽管这在统计学上不显著。HSVtk（联合更昔洛韦）和IFN-γ/GM-CSF基因联合使用，在局部肿瘤部位使肿瘤体积减少81%（p<0.01），在远处肿瘤部位使肿瘤体积减少43%（p<0.01）。因此，HSVtk和IFN-γ/GM-CSF基因治疗联合使用比单独使用任何一种治疗方法产生更大的治疗效果。