COMBINATION THERAPY WITH SUICIDE AND CYTOKINE GENES FOR HEPATIC METASTASES OF LUNG-CANCER

Metastases of lung cancer are a major cause of treatment failure, To e valuate the therapeutic efficacy of gene therapy in metastatic lung ca ncer, we used adenoviral (ADV) mediated transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene and the cytokine gene interleuki n-2 (IL-2) to treat a murine model of metastatic lung cancer in the li ver, Hepatic metastases were established by intrahepatic implantation of LL2 cells in syngeneic recipient mice. One week after tumor implant ation, various replication defective ADV vectors were injected intratu morally, Treatment with a vector expressing the HSV-tk followed by gan ciclovir 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, c ombination therapy with HSV-tk resulted in further tumor regression an d improvement of animal survival (p < 0.05), These results demonstrate that suicide and cytokine genes can be utilized in combination to tre at metastatic lung cancer in vivo.