Date of Award

2019

Embargo Period

8-1-2024

Document Type

Dissertation

Department

Microbiology and Immunology

College

College of Graduate Studies

First Advisor

Eric Bartee

Second Advisor

Arabinda Das

Third Advisor

Chrystal Paulos

Fourth Advisor

Paula Traktman

Abstract

Cancer is one of the world’s foremost causes of death, affecting over 15 million people. While traditional therapies offer some efficacy to patients novel treatments are needed to combat this epidemic. In recent years, novel immune- and combination-therapies have shown great strides in easing the cancer burden for some patients. One of these novel treatment modalities is oncolytic virotherapy, a form of immunotherapy which uses viruses with an inherent tumor specific tropism. Oncolytic virotherapy is an attractive option due to both its inherent immunotherapeutic potential as well as the ease by which it can be combined with other treatment modalities. Here, we studied both advantages using two tumor models which each pose a unique therapeutic challenge. First, we used a combination strategy including oncolytic Myxoma virus and traditional standard of care to treat glioblastoma multiforme. The results of this study showed that standard of care increased the spread of oncolytic virus both in vitro and ex vivo resulting in a synergistic therapeutic effect. Taken together these data suggests that this would be an effective combination for translation in vivo. Secondly, we sought to increase the spread of the oncolytic virus as a means to increase overall efficacy. By adding the fusion protein from a variety of other viruses into oncolytic myxoma virus we were able to produce a group of fusogenic constructs which induced syncytia formation during infection. Surprisingly, while these constructs looked promising in vitro, they displayed decreased efficacy in vivo negatively correlated to the viruses ability to form syncytia. These studies show the potential which myxoma has in synergizing with current therapeutic options, while also raising the question as to why some combinations may fail in vivo.

Rights

All rights reserved. Copyright is held by the author.

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