Survival and toxicity of xenogeneic murine retroviral vector producer cells in liver.
Murine retroviral vector producer cells (VPC) can selectively transfer genes stably into proliferating cells. We injected LacZ gene producing VPC directly into normal rat liver. There was no measurable gene transfer into the surrounding hepatic parenchyma with X-GAL staining. Rejection of the xenogeneic murine VPC occurred 7-14 days after injection. Toxicity of this delivery method was evaluated with the herpes simplex-thymidine kinase (HS-tk) gene, which confers sensitivity to the antiherpes drug, ganciclovir (GCV). HS-tk VPC were injected and allowed to grow in normal liver for 7 days before GCV treatment. There was no clinical or histologic evidence of toxicity with GCV treatment. These findings suggest that the direct injection of murine VPC into xenogeneic human tumors may survive sufficiently long without immunosuppression to transfer genes to tumor cells in situ without attendant toxicity.
Moorman
D W
DW
Human Gene Therapy Research Institute, Iowa Methodist Medical Center, Des Moines 50309.
Butler
D A
DA
Stanley
J D
JD
Lamsam
J L
JL
Ackermann
M R
MR
Jacobson
C D
CD
Culver
K W
KW
D000818:Animals; D002460:Cell Line; D017690:Cell Transplantation / Q000473:pathology*; D015774:Ganciclovir / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D012190:Retroviridae / Q000235:genetics*; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics; D014183:Transplantation, Heterologous / Q000473:pathology*
D013937:Thymidine Kinase; D015774:Ganciclovir