Heidi K. Baumgartner Wilson (1,3), Robert Hodges (2), Ginny Orndorff (3), and Margaret C. Neville (1,3)
(1) Department of Obstetrics & Gynecology and (2) Department of Biochemistry & Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA; (3) Claudin Technologies LLC, Aurora CO, USA.
Claudin-4 is a protein frequently overexpressed on the surface of tumors of epithelial origin, including the majority of ovarian tumors as well as cells thought to represent ovarian cancer stem cells. Claudin Technologies is developing a unique claudin mimic peptide (CMP) that significantly disrupts the activity of claudin-4 by binding to the surface of tumor cells, resulting in reduced tumor cell motility and increased cell death by apoptosis12-17. CMP is made of D-amino acids, making it resistant to proteolytic degradation. Injection of CMP into the peritoneal cavity of nude mice bearing human PEO4 ovarian tumors significantly reduced the rate of tumor progression and tumor cell apoptosis was increased 20-fold. CMP also induced apoptosis in human ovarian tumor slices freshly isolated from the operating room. Preliminary toxicity studies in mice show that doses of CMP injected IP or IV at 4 to 16 times the effective dose do not have detectable toxicities. The stability and preliminary safety and efficacy profiles of CMP suggest that it has promise as a therapeutic agent in ovarian cancer. Such targeted cancer therapies, used in appropriately selected patients, have the potential to significantly improve overall survival while avoiding unnecessary drug toxicity.