Novel Gene Delivery Technique for Organ Transplantation

Therapeutic options for hepatocellular carcinoma (HCC) are limited, and the results of therapy are dismal. Previous work from this laboratory demonstrated that cationic liposomes can deliver indicator transgenes to liver and lymphoid cells in vivo. We will apply these techniques to HCC by delivering transgenes that will directly kill hepatoma cells or modify the host's antitumor immunoinflammatory response. In Phase I, hepatoma specific promoters (e. g. alpha-fetoprotein) will be coupled to indicator genes to demonstrate the feasibility of the approach in vitro and in vivo. In Phase II, therapeutic transgenes will be constructed and tested in -an animal model of HCC. We hypothesize that local delivery of one or more transgenes controlled by a relatively HCC specific promoter will provide therapeutic benefit. Potential transgenes to be tested include: cytokines (e. g. TNFalpha, interferon , GM-CSF, IL2, chemotaxins), major histocompatibility antigens or metabolic enzymes. This therapeutic approach combining one or more of these transgenes with the cationic liposome delivery system will provide a novel and specific form of therapy for HCC.