Gene therapy for solid tumors.

Advances in molecular biology have proven that there is a genetic basis to the process of carcinogenesis that allows for the consideration of entirely new approaches to the treatment of cancer. The development of an ability to selectively destroy cancer cells through the manipulation of DNA may provide the opportunity to dramatically improve the quality of care and treatment of cancer patients by decreasing systemic toxicities and enhancing efficacy. These new therapies may occur through the restoration of genetic health, such as the insertion of normal tumor suppressor genes or via down-regulation of oncogene or growth factor receptor expression. Other possibilities include the targeting of genetic alterations in tumor cells that will enhance tumor immunogenicity or induce a specific sensitivity to a prodrug. In this chapter, we have reviewed the current status of gene therapy for solid tumors in the United States and evolving new approaches for this emerging clinical discipline.

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.