USE OF RECOMBINANT ADENOVIRUS TO TRANSFER THE HERPES-SIMPLEX VIRUS THYMIDINE KINASE (HSVTK) GENE TO THORACIC NEOPLASMS - AN EFFECTIVE IN-VITRO DRUG SENSITIZATION SYSTEM

Transfer of the herpes simplex virus thymidine kinase (HSVtk) gene int o tumor cells using retroviral vectors followed by administration of g anciclovir provides a potential strategy for the treatment of malignan cy. Because of the limitations of using retroviral vectors for clinica l application, the feasibility of using a recombinant adenovirus conta ining HSVtk was examined. Cell lines derived from human malignant meso theliomas and non-small cell lung cancers infected with a recombinant adenovirus containing HSVtk showed strong expression of HSVtk protein as determined by immunohistochemical staining. Infection with a recomb inant adenovirus containing HSVtk rendered cells sensitive to doses of ganciclovir that were 2-3 logs lower than uninfected cells or those i nfected with a control virus. A strong ''bystander effect'' was noted in mesothelioma lines; there was no diminution in the efficacy of ganc iclovir treatment until the ratio of infected:uninfected cells fell be low 1:10. This study thus demonstrates in vitro efficacy of an adenovi rus-transduced HSVtk drug sensitization gene therapy system in thoraci c malignancies. Recombinant adenovirus transfer of the HSVtk gene foll owed by ganciclovir may have promise as an in situ treatment for tumor s.