Browsing by Author "Bahlis, Nizar Jacques"

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    Enhancing the Anti-Tumour Immune Response of Reovirus with Sunitinib for the Treatment of Multiple Myeloma
    (2020-01) Meyers, Daniel E.; Morris, Don G.; Mahoney, Douglas J.; Bahlis, Nizar Jacques
    Multiple Myeloma (MM), a malignancy of plasma cells, is currently felt to be incurable. Current therapies such as monoclonal antibodies, immunomodulatory drugs, proteosome inhibitors, and autologous stem cell transplantation have substantially improved median overall survival over the past decade. However, despite the advent of these new therapeutic strategies the vast majority of MM patients relapse with therapy-resistant disease. The aim of this thesis was to determine the pre-clinical efficacy of reovirus (RV) as monotherapy and in combination with sunitinib (SUT) – a multi-tyrosine kinase inhibitor - for the treatment of MM. We utilized a syngeneic, immunocompetent, transplantable model of MM (Vk*MYC) for our lines of experimentation. Although our studies demonstrated that the addition of SUT to RV led to the modulation of immune subpopulations within the splenic tumour microenvironment, no clear data to support a definitive survival advantage with dual therapy were acquired. Despite the pre-clinical promise of RV for the treatment of MM, the addition of SUT does not appear to provide a survival advantage in this animal model. Given the modest of efficacy of SUT monotherapy in clinical studies of MM, this dual treatment approach should not be a priority for clinical investigation in MM at this time. Further pre-clinical studies are needed to better characterize the possible immunomodulatory role of SUT in MM.