Gene therapy for endometrial carcinoma with the herpes simplex thymidine kinase gene

We investigated whether retrovirus-mediated transfer of the herpes simplex thymidine kinase gene into a human endometrial carcinoma (EC4) cell line ca n sensitize these cells to the prodrug ganciclovir (GCV) and thereby provid e a therapeutic option for this cancer. A retrovirus encoding for the herpe s simplex virus tip-1 (HSV) thymidine kinase (tk) gene was generated in whi ch expression of tk is under control of the myeloproliferative sarcoma viru s (MPSV) promoter/enhancer. We used human mutated dihydrofolate reductase ( DHFR) cDNA as a selectable marker. Expression of tk was confirmed by Northe rn blot analysis and reverse transcription polymerase chain reaction. We de monstrated that the combination of retrovirally mediated tk gene transfer a nd GCV treatment effectively inhibits proliferation and causes death of EC4 cells in vitro. A bystander killing effect was observed when 90% of uninfe cted tumor cells were mixed with only 10% of HSVtk-infected cells, We sugge st that a gene therapy approach to endometrial carcinoma can be established using retroviral transfer of HSVtk to tumor cells and subsequent administr ation of GCV. (C) 2000 Academic Press.