Oncolytic Vesicular Stomatitis Virus and Sunitinib Combination Therapy for Treating Neuroblastoma
Abstract
Neuroblastoma is the most common extracranial solid tumour in infants and long-term survival for high-risk patients is below 50%. Generating antitumour immune responses have indicated potential. We hypothesized that sunitinib would modulate immune responses to improve oncolytic virus (VSVΔM51) productivity in the tumour and enhance the activity of antitumour immunity activated by VSVΔM51. Using an immunocompetent mouse model of neuroblastoma (neuro-2a), we found that VSVΔM51/sunitinib combination therapy elicited superior tumour regression and durable cure rates compared to either agent alone. We tested sunitinib’s ability to enhance infection in neuro-2a tumours, however, we found that infection with or without sunitinib was identical. We further tested whether sunitinib augmented antitumour immunity generated by VSVΔM51. We found that CD8+ T-cell depletion abolished the survival advantage elicited by VSVΔM51/sunitinib, indicating that sunitinib promoted adaptive immune responses. Collectively our results show that sunitinib improves VSVΔM51 therapy in neuro-2A tumours and is dependent on CD8+ T-cells.
Description
Keywords
Virology, Immunology, Oncology
Citation
Rakic, A. (2017). Oncolytic Vesicular Stomatitis Virus and Sunitinib Combination Therapy for Treating Neuroblastoma (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27174