Use of recombinant adenovirus to transfer the herpes simplex virus thymidine kinase (HSVtk) gene to thoracic neoplasms: an effective in vitro drug sensitization system.
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| Abstract |
Transfer of the herpes simplex virus thymidine kinase (HSVtk) gene into tumor cells using retroviral vectors followed by administration of ganciclovir provides a potential strategy for the treatment of malignancy. Because of the limitations of using retroviral vectors for clinical application, the feasibility of using a recombinant adenovirus containing HSVtk was examined. Cell lines derived from human malignant mesotheliomas 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 recombinant adenovirus containing HSVtk rendered cells sensitive to doses of ganciclovir that were 2-3 logs lower than uninfected cells or those infected with a control virus. A strong "bystander effect" was noted in mesothelioma lines; there was no diminution in the efficacy of ganciclovir treatment until the ratio of infected:uninfected cells fell below 1:10. This study thus demonstrates in vitro efficacy of an adenovirus-transduced HSVtk drug sensitization gene therapy system in thoracic malignancies. Recombinant adenovirus transfer of the HSVtk gene followed by ganciclovir may have promise as an in situ treatment for tumors.
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| Authors | W R Smythe, H C Hwang, K M Amin, S L Eck, B L Davidson, J M Wilson, L R Kaiser, S M Albelda |
| Journal | Cancer research (Cancer Res) Vol. 54 Issue 8 Pg. 2055-9 (Apr 15 1994) ISSN: 0008-5472 [Print] United States |
| PMID | 8174104 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
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