Regression of established macroscopic liver metastases after in situ transduction of a suicide gene.

摘要: The herpes simplex virus type 1 thymidine kinase (HSV1-TK) converts nontoxic nucleoside analogs such as ganciclovir into phosphorylated compounds that act chain terminators and specifically kill dividing cells. This property could be exploited for the treatment of tumors are made up rapidly cells invading a nonproliferating tissue. For this purpose, specific expression suicide gene tumor can further targeted by using retroviral-mediated transfer. We investigated whether direct intratumoral transduction might induce elimination malignant solid tumors. Rats with established macroscopic liver metastases were given an injection packaging producing either HSV1-TK- or lacZ-expressing recombinant retroviral particles. All rats next treated ganciclovir. A dramatic regression volume was observed in HSV1-TK-treated animals. residual mostly massive fibrotic reaction, mean cancer cell mass being reduced approximately 60-fold compared to controls. In some animals, devoid efficacy appears part due "bystander effect" which transferred from active local immune reaction evidenced infiltration macrophages both CD4+ CD8+ lymphocytes. efficient therapeutic approach ultimate disseminated humans also applied large variety