Date of Award

12-2016

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. Cindy L. Linn

Second Advisor

Dr. Karim Essani

Third Advisor

Dr. Rob Eversole

Keywords

Oncolytics, retinoblastoma, cancer, virotherapy, tanapoxvirus

Access Setting

Masters Thesis-Open Access

Abstract

Retinoblastoma is the leading cause of intraocular malignancy in children under 2 years of age. Current treatments, while generally effective in eliminating the tumor, have many negative side effects. Oncolytic virotherapy is the use of either wild type or recombinant viruses, to destroy tumor cells. There are currently several viruses being engineered as potential therapeutics for a wide range of cancers. They offer tumor specific alternative to current therapies with lesser toxicity. This study looked at the oncolytic efficacy of multiple tanapoxviruses (TPV) recombinants in an in vitro retinoblastoma. Here we have tested recombinants of TPV for their ability to replicate in two retinoblastoma cell lines; Y-79 and WERI-RB1. To ascertain if engineered oncolytic TPV could affect retinoblastoma cells in vitro, multiple different assays were used, testing replication competence of virus, ability to express transgenes and induce cell death. Single step replication studies using two multiplicities of infections (MOIs) of each virus and their dose dependent effect on cell viability was investigated. Our results demonstrated that retinoblastoma cells were successfully infected, transgenes were expressed, competent replication occurred at both MOIs and all viruses caused a significant decrease in the number of living cells and demonstrated that the virus lysed the tumor cells. These results show engineered TPVs and recombinants to be a potential candidate as a onocolytic virotherapy for retinoblastoma.

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