Description

Oncolytic virus-mediated immunotherapy

Marie-Claude Bourgeois-Daigneault^1*, Dominic Guy Roy¹, Amelia Sadie Aitken¹, Theresa Falls¹, John Cameron Bell¹

¹ Ottawa Hospital Research Institute, Centre for Innovative Cancer Research, Ottawa, Ontario, K1H 8L6

^* Corresponding author

The lack of treatment options for patients with chemotherapy-resistant cancers is pushing forward the rapid development of alternative therapies. One such option, especially for disseminated or recurrent diseases, is the use of oncolytic viruses, with the first candidate now approved for the use in patients. Oncolytic viruses are known to specifically destroy tumors by mediating direct killing and tumor vascular shutdown, but the induction of an efficient and persistent anti-tumor immune response is a facet that is underappreciated. Using the clinical trial candidate rhabdovirus Maraba-MG1 in orthotopic murine breast tumor models where tumors are surgically resected and the animals are rechallenged, we demonstrate here the importance of this immune response. Our results show that the administration of MG1 is sufficient to control the growth of subsequent tumors and even cure some animals without the need for further treatments. The virus induces an efficient tumor-specific immune response and recruits immune cells to the tumor. Also, tumor-infiltrating lymphocytes are able to penetrate the tumor more profoundly. Importantly, treatment with MG1 causes the upregulation of PDL1 by tumor cells and active regulatory T cells were found in greater amounts. Given the recent success of immune checkpoint inhibitors, we investigated if this second treatment could further improve oncolytic virotherapy. Indeed, our data demonstrate the successful combination of MG1 with immune checkpoint inhibitors in tumor models that are usually resistant to the latter. We believe that our study is the first to reveal the extent of the potential of oncolytic viruses as immunotherapeutic agents.