Oncolytic Vesicular Stomatitis Virus and Sunitinib Combination Therapy for Treating Neuroblastoma

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atmire.migration.oldid6090
dc.contributor.advisorBeaudry, Paul
dc.contributor.advisorMahoney, Douglas
dc.contributor.authorRakic, Andrea
dc.contributor.committeememberMorris, Donald
dc.contributor.committeememberLiao, Shan
dc.contributor.committeememberStrother, Douglas
dc.date.accessioned2017-09-29T19:58:05Z
dc.date.available2017-09-29T19:58:05Z
dc.date.issued2017
dc.date.submitted2017en
dc.description.abstractNeuroblastoma 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.en_US
dc.identifier.citationRakic, 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/27174en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/27174
dc.identifier.urihttp://hdl.handle.net/11023/4183
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectVirology
dc.subjectImmunology
dc.subjectOncology
dc.subject.otherNeuroblastoma
dc.subject.otherTumour microenvironment
dc.subject.otherOncolytic virus
dc.subject.otherImmunotherapy
dc.subject.otherSunitinib
dc.titleOncolytic Vesicular Stomatitis Virus and Sunitinib Combination Therapy for Treating Neuroblastoma
dc.typemaster thesis
thesis.degree.disciplineMedical Science
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
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