Enhancing Oncolytic Rhabdovirus Infection With Sunitinib In An IFN Responsive Tumour Model

Date
2016
Journal Title
Journal ISSN
Volume Title
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Abstract
Oncolytic virus (OV) therapy for cancer is an emerging biotherapeutic strategy that employs replicating viruses to selectively infect and kill cancer cells. While promising, host innate immunity, namely type I IFN signaling, remains a barrier to OV therapy as it eliminates the virus before it spreads efficiently through the tumour. Sunitinib (Su), a receptor tyrosine kinase inhibitor, was recently shown to enhance OV infection by inhibiting IFN signaling in tumour cells. We therefore hypothesized that Su might enhance oncolytic rhabdovirus (ORV) infection in tumours. Indeed, Su treatment improved ORV productivity, tumour regression and overall survival in an IFN responsive tumour model. Su reduced the number and function of IFN producing myeloid cells such as cDCs and MΦ and thereby improved tumour infection with ORV. Collectively, our findings provide further support for the clinical evaluation of Su/ORV co-therapy in OV refractory tumors.
Description
Keywords
Virology, Immunology, Oncology
Citation
Dastidar, H. (2016). Enhancing Oncolytic Rhabdovirus Infection With Sunitinib In An IFN Responsive Tumour Model (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25906