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 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.
Smythe
W R
WR
Department of Surgery, University of Pennsylvania, Philadelphia.
Hwang
H C
HC
Amin
K M
KM
Eck
S L
SL
Davidson
B L
BL
Wilson
J M
JM
Kaiser
L R
LR
Albelda
S M
SM
D000256:Adenoviridae; D002289:Carcinoma, Non-Small-Cell Lung; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015774:Ganciclovir / Q000633:toxicity*; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms; D008654:Mesothelioma; D011995:Recombination, Genetic; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013899:Thoracic Neoplasms; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
D013937:Thymidine Kinase; D015774:Ganciclovir