Life Sciences Seminar: Enhancing VSV for Oncolytic Virus Therapy: A Transcriptomic Approach to Decipher Primed Resistance by Some Prostate Cancer

Life Science Seminar
Enhancing VSV for Oncolytic Virus Therapy: A Transcriptomic Approach to Decipher Primed Resistance by Some Prostate Cancer

Alaa Abdelmageed Ahmed (Biotechnology ’20)
Genetics Ph.D. Candidate
University of Rochester                            

Abstract:
Vesicular Stomatitis Virus (VSV) has been suggested for use as an oncolytic agent, due to its wide host range and its ability to suppress host antiviral responses. Conceptually, a good oncolytic agent can selectively kill cancer cells while sparing normal healthy ones. It is believed that antiviral signaling pathways are perturbed in most cancer cells, rendering them susceptible to selective killing by VSV. However, some cancer cells still retain an intact antiviral response and are therefore “resistant” to oncolysis. Our previous work suggests NFkB-dependent antiviral signaling responsible for the inherent resistance to VSV in resistant human prostate cancer (PrCa) cells. Here, we follow-up our previous findings with a transcriptomic approach (RNAseq) to identify targets underlying resistance vs sensitivity in two well-established human PrCa cell-lines (LNCaP and PC3 cells) infected with wild-type and mutant VSV strains. Our results show that the resistant cells (PC3) are pre-armed with high expression of inflammatory genes in comparison to the sensitive ones (LNCaP). Moreover, upon infection with VSV, PC3 cells exhibit enrichment of several antiviral pathways and upregulation of multiple antiviral and type-I interferon target genes (eg. IL6, IL1B, CXCL8). In addition to multiple genes upstream of the NFkB pathway, these target genes are perfect candidates for shRNA knock-down experiments. Validation of such targets through functional confirmation would provide another layer of confidence in the underlying cause of resistance to VSV in PrCa cells. The significance of this research lies in understanding host responses to VSV in cancer and therefore paving the way to enhancing VSV’s use as an oncolytic agent, especially for better customization of individualized therapies.

Intended Audience:
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