Treatment of experimental liver tumors by in vivo suicide gene transfer in rats

: We investigated whether the transduction of a suicide gene might induce the elimination of malignant solid tumours. BDIX male rats were given an intra-hepatic injection of a mixture containing DHDK12 tumor cells and xenogeneic fibroblasts. The latter were producing either the herpes simplex virus type 1 thymidine kinase HSV1-TK- or nls-lac Z(control)-expressing recombinant retroviral particles. 5 days later, a time at which the tumor is macroscopic, all the rats were treated with ganciclovir, a nucleoside analog that is metabolized by HSV1-TK into a toxic compound. After 5 days of treatment, a dramatic reduction in tumour volume was noted in the HSV1-TK group. These results delineate a new therapeutical strategy for the treatment of disseminated liver metastases or of a large variety of solid malignant tumours.