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SUSCEPTIBILITY OF GLIOBLASTOMA CELLS TO ONCOLYTIC VESICULAR STOMATITIS VIRUS

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abstract
Glioblastoma (GBM) is the deadliest type of brain tumor with very poor survival rates. Thus, GBM patients are candidates for novel therapies such as oncolytic virus therapy. Vesicular stomatitis virus (VSV) is a highly cytolytic virus with tropism for cancer cells with attenuated interferon mediated antiviral mechanisms. Recombinant VSV, whose envelope glycoprotein is substituted with that of Lassa virus (Lassa-VSV), is safer for intracranial injection compared to VSVs with wild type VSV glycoprotein, such as oncolytic M51R M protein mutant VSV (M51R-VSV). Oncolytic activity of Lassa-VSV and M51R-VSV was analyzed by MTS assays of cell viability in three patient-derived GBM cell lines from Wake Forest Baptist Medical Center. GBM cell lines were also analyzed by immunoblots to test the hypothesis that variations in susceptibility are due to expression of interferon-stimulated genes (ISGs) and/or apoptosis-regulating gene products. The results indicate that all three lines were susceptible to Lassa-VSV, but different GBM cell lines varied in susceptibility to Lassa-VSV infection. Unexpectedly, the most sensitive cell line expressed ISGs, but also expressed more pro-apoptotic protein BAX. These results indicate that the levels of expression not only of ISGs but also of apoptosis-regulating gene products may be involved in mediating susceptibility to oncolytic Lassa-VSV therapy.
subject
Apoptosis-regulating genes
BAX
Glioblastoma
Glycoprotein
Interferon stimulated genes
Vesicular stomatitis virus
contributor
ZHANG, KAILONG (author)
Lyles, Douglas (committee chair)
Ornelles, David (committee member)
Hollis, Thomas (committee member)
date
2020-05-29T08:35:55Z (accessioned)
2020-05-29T08:35:55Z (available)
2020 (issued)
degree
Biomedical Science – MS (discipline)
identifier
http://hdl.handle.net/10339/96816 (uri)
language
en (iso)
publisher
Wake Forest University
title
SUSCEPTIBILITY OF GLIOBLASTOMA CELLS TO ONCOLYTIC VESICULAR STOMATITIS VIRUS
type
Thesis

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