297. Radiovirotherapy in Ovarian Cancer Using Recombinant Measles Expressing Sodium Iodide Symporter

Abstract

We have shown that the MV-Edm, a vaccine strain of measles virus, is potently oncolytic for many types of tumor cells but causes minimal damage on normal cells. Phase I clinical trial in ovarian cancer using recombinant measles virus which express soluble CEA for non-invasive monitoring of the profiles of viral gene expression is on-going in our institution. We are continuing to improve the efficacy and accuracy of MV-Edm for virotherapy for ovarian cancer. Ovarian cancer is radiosensitive; several clinical trials of intraperitoneal radioimmunotherapy, representing the use of radionuclide conjugated to monoclonal antibodies for imaging and therapy, have shown promising results. We previously generated a recombinant measles virus expressing the human thyroidal sodium iodide symporter (MV-NIS). Myeloma tumor cells infected by MV-NIS very efficiently traps radioiodine and allows non invasive imaging of sites of viral gene expression. The aim of this study is to evaluate the potential of MV-NIS for virotherapy for ovarian cancer, especially for elimination of advanced residual disease. MV-NIS has selective oncolytic activity; when we infected ovarian cancer cell lines using MV-NIS, large multinucleated syncytia were seen in the cancer cells but not in peripheral blood mononuclear cells. Ovarian cancer cell lines SKOV3ip1 and IGROV-1 infected with MV-NIS efficiently accumulated 125I. The uptake was 20 to 40 times higher compared to uninfected cells, and was inhibited by more than 90% using a specific inhibitor KClO4. These results are very encouraging and we are currently performing in vivo experiments in an orthotopic model of ovarian cancer to evaluate the potential of MV-NIS for therapy of advanced stage ovarian cancer.