Oxidative Stress Renders T Cells Susceptible To Oncolytic Virus Infection

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University of Guelph

Oncolytic viruses selectively infect and kill cancer cells and induce tumour-specific immune responses. However, success has been limited partially due to the ability of some oncolytic viruses, like vesicular stomatitis virus (VSV) to cause off-target infection of leukocytes, including activated T cells, thereby reducing therapeutic potential. This could be problematic for multi-dosing protocols in which the first dose of VSV activates T cells that can then be infected with subsequent doses of the virus. The aim of the research presented in this thesis was to investigate potential mechanisms behind off-target infection of T cells by VSV, as well as ways to abrogate this infection, both in vitro and in vivo, to improve VSV-based cancer immunotherapies. All research was summarized in manuscript format to facilitate publication.

oncolytic virotherapy, cancer immunotherapy, oxidative stress