Improving Oncolytic Virotherapy Using Vanadium Compounds
Anabel Bergeron1,2, Mohammed Selman1,2, Andrew Chen1, Fanny Tzelepis1, Joel Werier3, Hesham Abdelbary3, Jean-Simon Diallo1,2*
1Centre for Innovative Cancer Research, Ottawa Hospital Research Institute; 2Department of Biochemistry, Microbiology and Immunology, University of Ottawa; 3Department of Surgery Orthopaedics, Ottawa Hospital
Sarcomas are a lethal form of cancer that stem from mesenchymal tissues and comprises connective tissue, cartilage, bone and muscle tumors. While some cancers, have gained significant therapeutic momentum, progress in the field of sarcomas seems to be virtually stagnant - survival rates of osteosarcoma patients have remained essentially unchanged in the last three decades. Immunotherapies have emerged as a robust treatment paradigm, having improved the prognosis of a broad range of malignancies such as melanoma, lung and renal cell cancers. However immune-based therapies like immune checkpoint inhibition, vaccines and cytokine-based therapies have not yet translated into meaningful outcomes in the clinic for sarcoma patients. Oncolytic virotherapy (OV) is a novel branch of immunotherapy that employs viruses with engineered oncotropism to selectively target and kill cancer cells as well as stimulate an antitumor immunity. Our group has recently reported that vanadium-based protein tyrosine phosphatase (PTP) inhibitors improve viral oncolysis as well as long-term antitumor immunity and survival when used in conjunction with oncolytic VSV∆51 in syngeneic glioma and carcinoma tumor models. Given that VSV∆51 can specifically target, replicate and kill sarcoma cell lines, we sought to evaluate the impact of the combination of VSV∆51 and vanadate in a sarcoma model. Upon infection, vanadate enhanced viral spreading and cytotoxicity in canine, murine and human sarcoma cell lines. The combination therapy improved infection and survival in intraperitoneal and subcutaneous syngeneic models. Delayed tumor progression was also observed. Furthermore, the combination increased viral infection ex vivo in excised human xenograft tumors. Overall, this project supports the translational potential of vanadium compounds paired with oncolytic virotherapy for the treatment of sarcomas.
Funding: Terry Fox Research Institute, Valerie's Flutter Foundation