Date of Award

5-2015

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. Karim Essani

Second Advisor

Dr. Yan Lu

Third Advisor

Dr. Bruce Bejcek

Access Setting

Masters Thesis-Open Access

Restricted to Campus until

5-15-2025

Abstract

Since the emergence of oncolytic viruses (OVs), OVs have seen success in clinical trials and are a vital alternative treatment for cancer. Colorectal cancers are diseases which cause substantial health issues in the developed world, but current invasive treatment methods do not perform well in patients with advanced disease. We have explored the potential of tanapoxvirus (TPV) for its oncolytic virothrapy in two manners; specific gene deletion and non-targeted gene deletion. The non-targeted mutation of TPV’s genome was attempted using N-methyl-N-nitro-N-nitrosoguanidine (NTG) and N-ethyl-N-nitrosourea (ENU) as alkylating chemical. Specific gene deletion involved knocking-out a thymidine kinase gene (TPV-66R) and a TNF suppressor gene (TPV-2L) from TPV’s genome and inserting bacetrial flagellin gene. This double knock-out TPV was assessed in vivo involving athymic mice. Subcutaneously, 5 x 106 HCT-116 cells were injected in athymic nude mice and successively treated by a single intratumoral injection. Statistically significant reduction was observed in tumors which received a dose of TPV/Δ2L/Δ66R::fliC and TPV/Δ2L. Our data points to a promising direction for OVs and based on our results we suggest TPV mutants equipped with host immune stimulators could be an alternative viral treatment for cancer.

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