TARGETING OVARIAN CANCER INITIATING CELLS WITH ONCOLYTIC REOVIRUS AND LENTIVIRAL TRAIL GENE DELIVERY

Abstract

The relapse of ovarian cancer may be caused by ovarian cancer stem cells (OCSCs), a minority of cells within a tumor. Currently, there are no available therapies that target these cells. OCSCs are drug and radiation resistance, so alternate methods of eradicating these cells must be explored. We will investigate the effect of using an oncolytic virus in conjunction with a therapeutic transgene on OCSCs in vitro. A population of OCSCs will be subject to infection with reovirus, a human virus that is inherently oncolytic. This will be followed with selective lentiviral gene delivery of Tumor Necrosis Factor (TNF)-Related Apoptosis Inducing Ligand (TRAIL), an anti-cancer agent that induces apoptosis only in cancer cells, to cells expressing CD133, a putative OCSC marker. A lentiviral vector will be constructed using a single chain antibody (scFv) that selectively binds to the CD 133 epitope on OCSCs. TRAIL may work synergistically with reovirus to induce apoptosis in OCSCs. This interaction and the incidence of apoptosis will be observed and measured. The results of this project may be applied to future in vivo studies.