Limitations of retrovirus-mediated HSV-tk gene transfer to pulmonary adenocarcinoma cells in vitro and in vivo.
The utility of conferring chemosensitivity to pulmonary adenocarcinoma tumor cells by retrovirus-mediated transfer of herpes simplex virus thymidine kinase (HSV-tk) gene was assessed in vitro and in vivo. Retrovirus-mediated HSV-tk gene transfer to human adenocarcinoma cells (A549 cells) or mouse lung epithelial carcinoma cells (MLE cells) resulted in expression of HSV-tk mRNA and sensitivity to ganciclovir (GCV) in vitro. In nude mice, tumors produced from HSV-tk transduced MLE-7 cells regressed after 14 days of GCV treatment. However, in residual tumors, the size of the HSV-tk mRNA was altered and the sensitivity to further GCV treatment decreased. Tumor regression following GCV treatment was not observed in nude mice bearing HSV-tk-infected adenocarcinoma cells, MLE-15 and A549. Intratumor injection of HSV-tk producer cells failed to transfer HSV-tk gene to the A549 tumor cells in vivo. The lack of a 'bystander' effect, failure to achieve tumor regression, and loss of GCV sensitivity in some tumors in vivo may limit the utility of HSV-tk for therapy of pulmonary adenocarcinoma.
Zhang
L
L
Children's Hospital Medical Center, Division of Pulmonary Biology, TCHRF, Cincinnati, OH 45229, USA.
Wikenheiser
K A
KA
Whitsett
J A
JA
D000230:Adenocarcinoma / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D015152:Blotting, Northern; D015774:Ganciclovir / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics*; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D012333:RNA, Messenger; D013937:Thymidine Kinase; D015774:Ganciclovir