SURVIVAL AND TOXICITY OF XENOGENEIC MURINE RETROVIRAL VECTOR PRODUCERCELLS IN LIVER

Murine retroviral vector producer cells (VPC) can selectively transfer genes stably into proliferating cells. We injected LacZ gene producin g VPC directly into normal rat liver. There was no measurable gene tra nsfer into the surrounding hepatic parenchyma with X-GAL staining. Rej ection of the xenogeneic murine VPC occurred 7-14 days after injection . Toxicity of this delivery method was evaluated with the herpes simpl ex-thymidine kinase (HS-tk) gene, which confers sensitivity to the ant iherpes drug, ganciclovir (GCV). HS-tk VPC were injected and allowed t o grow in normal liver for 7 days before GCV treatment. There was no c linical or histologic evidence of toxicity with GCV treatment. These f indings suggest that the direct injection of murine VPC into xenogenei c human tumors may survive sufficiently long without immunosuppression to transfer genes to tumor cells in situ without attendant toxicity. (C) 1994 Wiley-Liss, Inc.