We evaluated the antitumor effects of combination gene therapy on CT26 mouse colon cancer cells, using the genes for herpes simplex virus thymidine kinase gene HSV-TK combined with granulocyte macrophage colony-stimulating factor (GM-CSF) compared with HSV-TK alone. Cells, unmodified or retrovirally transduced with HSV-TK or GM-CSF, were inoculated subcutaneously into syngeneic BALB/c mice in various combinations. HSV-TK and GM-CSF were also delivered using different routes (in separate cells vs doubly transfected single cells). Both HSV-TK (with i.p. ganciclovir - GCV - treatment) and GM-CSF genes had independent antitumor effects, and given together they caused significant reduction in tumor volumes compared with the HSV-TK gene alone (P < 0.001). Following GCV treatment, however, the treated/control ratios for tumor volumes were not different between tumors containing either HSV-TK alone or both genes (0.27 vs 0.25, respectively). Thus, the presence of GM-CSF did not increase the bystander effect of HSV-TK. Tumors receiving genes transferred in separate cells tended to be more consistently suppressed after GCV treatment than when both genes were transferred in the same cells, although this was not statistically significant. Thus, combination GM-CSF and HSV-TK gene therapy produced greater therapeutic efficacy than HSV-TK alone, but the bystander effect was not enhanced by GM-CSF.

中文翻译：

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单纯性疱疹病毒胸苷激酶和粒细胞巨噬细胞集落刺激因子联合基因治疗在小鼠CT26细胞结肠癌模型中的应用。

我们使用单纯疱疹病毒胸苷激酶基因HSV-TK结合粒细胞巨噬细胞集落刺激因子（GM-CSF）与单纯HSV-TK的基因，评估了联合基因疗法对CT26小鼠结肠癌细胞的抗肿瘤作用。将未修饰或逆转录病毒HSV-TK或GM-CSF转导的细胞以各种组合皮下接种到同系BALB / c小鼠中。HSV-TK和GM-CSF也使用不同的途径递送（在单独的细胞与双重转染的单细胞中）。HSV-TK（ip更昔洛韦-GCV-治疗）和GM-CSF基因均具有独立的抗肿瘤作用，并且与单独的HSV-TK基因相比，它们共同导致肿瘤体积显着减少（P <0.001）。但是，经过GCV处理后，在单独含有HSV-TK或两个基因的肿瘤之间，肿瘤体积的治疗/对照率没有差异（分别为0.27和0.25）。因此，GM-CSF的存在并未增加HSV-TK的旁观者效应。与在相同基因中转移两个基因时相比，接受在单独细胞中转移的基因的肿瘤倾向于比在相同基因中转移两个基因时受到更一致的抑制。因此，联合使用GM-CSF和HSV-TK基因疗法比单独使用HSV-TK产生更大的治疗效果，但GM-CSF并未增强旁观者的作用。与在相同基因中转移两个基因时相比，接受在单独细胞中转移的基因的肿瘤倾向于比在相同基因中转移两个基因时受到更一致的抑制。因此，联合GM-CSF和HSV-TK基因疗法比单独使用HSV-TK产生更大的治疗效果，但GM-CSF并未增强旁观者的作用。与在相同基因中转移两个基因时相比，接受在单独细胞中转移的基因的肿瘤倾向于比在相同基因中转移两个基因时受到更一致的抑制。因此，联合GM-CSF和HSV-TK基因疗法比单独使用HSV-TK产生更大的治疗效果，但GM-CSF并未增强旁观者的作用。