Research Project
2429585
In Phase I studies we developed key technologies for non-viral gene therapy directed at epithelial cells. These include (i) gene expression systems based on regulatory elements from the keratin 6 gene that provides-high level expression and (ii) gene delivery systems based on administration by jet injection. We propose to apply these advances to the development of non-viral gene therapies for epithelial tumors with high morbidity and poor prognosis. We will develop gene medicines that transduce tumors in vivo with suicide genes and/or immunogenic genes to achieve both reduction in tumor mass and immune surveillance. We will use the keratin K6-based expression system to achieve high-level, tissue- specific expression within proliferating tumor cells without affecting normal epithelia. We will use proprietary DNA/liposome complexes and DNA/peptide completes for gene delivery to tumor cells after jet injection. These systems will be tested in conventional syngeneic models and a unique transgenic animal model. The goal of these studies is to develop gene medicines for clinical trials. PROPOSED COMMERCIAL APPLICATION: SCC of the head & neck accounts for 5% of all malignancies. SCC of the lung represents 30% of lung cancer. Both tumors have a poor prognosis. Cutaneous SCC is the most common malignancy and the incidence is increasing. While treatable by excision, a prophylactic vaccine would be clinically important to prevent recurrence and metastasis. The market potential in US and EU with conservative estimates of penetrance and pricing is >$l ,000 M.
