Oncolytic Reovirus Combined with Sunitinib as a Novel Multi-Mechanistic Treatment Strategy for Renal Cell Carcinoma

Abstract

Metastatic renal cell carcinoma (RCC) is an incurable disease resistant to both radiation and cytotoxic chemotherapy. Although new molecularly targeted agents have increased the therapeutic options for patients with this disease, 5-year overall survival rates remain below 10%. The aim of this thesis was to determine the preclinical efficacy of reovirus as a monotherapy and in combination with sunitinib, a first line mRCC agent and multi-tyrosine kinase inhibitor, for the treatment of RCC. To assess this, studies employing a panel of RCC cell lines, as well as a syngeneic immunocompetent murine model of RCC were utilized. Collectively, these studies demonstrate that reovirus is both a novel oncolytic and immunotherapeutic agent against RCC. Furthermore, our results provide the first evidence that sunitinib augments the anti-tumour immune response generated by an oncolytic virus. As such, this novel treatment paradigm has immediate clinical applicability for use against multiple tumour histologies, particularly RCC.