Recombinant Epithelial Junction Opener Protein for Enhanced Drug Penetration in Epithelial Tumors

University of Washington (Principal Investigator: Andre Lieber, MD, PhD)

This proposal aims to break down a major barrier to treating ovarian cancer. Recurrent ovarian cancer is often resistant to treatment because chemotherapy drugs, such as Doxil, penetrate tumors poorly. This means that more distant tumor cells receive low drug concentrations and survive chemotherapy. One of the reasons for poor drug penetration is that tumor cells form a barrier of tight junctions. We have developed a small recombinant protein to open tight junctions and allow greater accessibility of chemotherapy molecules. When we tested our junction openers (“JO”) along with chemotherapy drugs in mice, we were able to completely eliminate the tumor in most animals. We also demonstrated excellent safety of this approach in monkeys when we tested JO in combination with Doxil at doses that we would use in patients. We propose a phase I/II clinical trial with JO and Doxil in women with recurrent ovarian cancer. The primary goal of this trial is to confirm the safety of the treatment and evaluate therapeutic responses. Furthermore, we will use serum samples and, if available tumor biopsies, to learn more about the interaction of JO with the body and the tumor. We expect to demonstrate that the treatment is safe with increased efficacy of Doxil treatment. This new approach will not only result in better outcomes for ovarian cancer patients but can also potentially be expanded to treat other patients with solid tumor cancers.