dc.contributor.author | Nickerson, Rhea | |
dc.date.accessioned | 2023-03-02T14:57:01Z | |
dc.date.available | 2023-03-02T14:57:01Z | |
dc.date.issued | 2023-03-01 | |
dc.identifier.uri | http://hdl.handle.net/10222/82326 | |
dc.description.abstract | Advanced melanoma is highly metastatic and resistant to chemotherapies, with a 5-year survival rate below 30%. This study investigated Natural Killer T (NKT) cell-based immunotherapy in combination with oncolytic vesicular stomatitis virus (VSV-ΔM51). VSV-ΔM51 infection increases production of CXCR3 ligands CXCL9, -10, and -11, potentially recruiting CXCR3-expressing NKT cells into the tumor microenvironment; however, the specific role of the CXCR3 axis in treatment efficacy is unknown. Responses to VSV-ΔM51 and NKT cell immunotherapy were tested using a melanoma model. Combined treatments enhanced survival duration compared to monotherapies in both wild-type and CXCR3-/- mice. Loss of CXCR3 impaired accumulation of NKT cells within tumors, but did not impair other immune populations. CXCR3-/- mice exhibited improved responses to VSV-ΔM51, with increased viral persistence post-treatment. These results demonstrate that combined VSV-ΔM51 and NKT cell immunotherapy provides superior survival benefits compared to monotherapies. However, the CXCR3 axis appears ultimately dispensable for combined therapy. | en_US |
dc.language.iso | en | en_US |
dc.subject | Immunology | en_US |
dc.title | Role of the CXCR3 Chemokine Receptor Axis in the Combination of Oncolytic Vesicular Stomatitis Virus Therapy and Natural Killer T Cell Immunotherapy in Melanoma | en_US |
dc.type | Thesis | en_US |
dc.date.defence | 2023-01-30 | |
dc.contributor.department | Department of Microbiology & Immunology | en_US |
dc.contributor.degree | Master of Science | en_US |
dc.contributor.external-examiner | Roy Duncan | en_US |
dc.contributor.graduate-coordinator | Zhenyu Cheng | en_US |
dc.contributor.thesis-reader | Jean Marshall | en_US |
dc.contributor.thesis-reader | Andrew Stadnyk | en_US |
dc.contributor.thesis-supervisor | Brent Johnston | en_US |
dc.contributor.ethics-approval | Received | en_US |
dc.contributor.manuscripts | No | en_US |
dc.contributor.copyright-release | No | en_US |