Kwong Y L, Chen S H, Kosai K, Finegold M, Woo S L
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA.
Chest. 1997 Nov 5;112(5):1332-7. doi: 10.1378/chest.112.5.1332.
Metastases of lung cancer are a major cause of treatment failure. To evaluate the therapeutic efficacy of gene therapy in metastatic lung cancer, we used adenoviral (ADV) mediated transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene and the cytokine gene interleukin-2 (IL-2) to treat a murine model of metastatic lung cancer in the liver. Hepatic metastases were established by intrahepatic implantation of LL2 cells in syngeneic recipient mice. One week after tumor implantation, various replication defective ADV vectors were injected intratumorally. Treatment with a vector expressing the HSV-tk followed by ganciclovir administration with ADV.tk resulted in significant regression of tumor (p<0.01) as well as prolongation of survival (p<0.001). While a vector expressing mouse IL-2 ADV.IL-2 alone was ineffective, combination therapy with HSV-tk resulted in further tumor regression and improvement of animal survival (p<0.05). These results demonstrate that suicide and cytokine genes can be utilized in combination to treat metastatic lung cancer in vivo.
肺癌转移是治疗失败的主要原因。为了评估基因治疗在转移性肺癌中的疗效，我们使用腺病毒（ADV）介导单纯疱疹病毒胸苷激酶（HSV-tk）基因和细胞因子基因白细胞介素-2（IL-2）的转移，来治疗肝转移性肺癌小鼠模型。通过在同基因受体小鼠肝内植入LL2细胞建立肝转移模型。肿瘤植入一周后，将各种复制缺陷型ADV载体瘤内注射。用表达HSV-tk的载体治疗，随后给予更昔洛韦与ADV.tk联合使用，导致肿瘤显著消退（p<0.01）以及生存期延长（p<0.001）。虽然单独使用表达小鼠IL-2的载体ADV.IL-2无效，但与HSV-tk联合治疗导致肿瘤进一步消退和动物生存期改善（p<0.05）。这些结果表明，自杀基因和细胞因子基因可联合用于体内治疗转移性肺癌。
