The principal focus of this proposal is to explore the feasibility of using Salmonella to deliver EGF peptide antagonist to solid tumors as an anti- tumor agent. Small peptides that inhibit the activity of growth factor ligands have recently attracted significant interest in cancer therapy. As a result of the discovery of tumor-targeting Salmonella, these peptides are now pharmaceutically tractable. We have expressed potato carboxypeptidase inhibitor (PCI), a 39 amino acid peptide antagonist of EGF in a tumor-targeting Salmonella strain. Preliminary results demonstrate the ability of recombinant PCI to enhance the anti-tumor activity of Salmonella in vitro. We propose to further investigate, optimize and generate a robust tumor-targeting Salmonella strain stably expressing recombinant PCI with significant anti-cancer activity in vivo. A team of diverse and highly experienced scientists will assure the success of this project. Since the EGF receptor is over-expressed in many epithelial carcinomas, we exp3ect that PCI will have a wide application in the treatment of breast, lung, skin and prostate cancer. This system could potentially be the most expedient and less expensive way to produce biologically active recombinant antagonist in situ. The magnitude of the need for a tool for systemic delivery of growth factor antagonists is huge so as to create an enormous market potential for cancer therapeutics. PROPOSED COMMERCIAL APPLICATIONS: Tumor targeting Salmonella provides a system to produce, secrete and deliver peptide antagonists to tumor cells therapy providing an effective and less expensive way to produce recombinant proteins at the tumor site. The magnitude of the need for a tool for systemic delivery of peptides is huge so as to create an enormous market potential for cancer therapeutics.
Thesaurus Terms: Salmonella, antineoplastic, epidermal growth factor, gene delivery system, growth factor receptor, transfection /expression vector enzyme inhibitor, gene therapy biotechnology, laboratory mouse, molecular cloning, neoplastic cell
