Date of Award

4-2013

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. Karim Essani

Second Advisor

Dr. Bruce Bejcek

Third Advisor

Dr. Brian Tripp

Access Setting

Masters Thesis-Campus Only

Restricted to Campus until

4-15-2033

Abstract

Cancer remains a major health problem despite the advances in conventional cancer therapy. Remarkable advances in molecular biology and genetic engineering have improved the possibility of a novel cancer treatment using animal viruses, called oncolytic viruses. Patients receiving this kind of therapy may develop immunity against the viral therapy, thereby limiting the extended use of the same oncolytic virus multiple times. As such, a large pool of oncolytic viruses must be available for the success of such a therapy. Here, we describe several Tanapoxvirus (TPV) mutant viruses designed for this purpose. TPVK02LmCherry is a genetically modified TPV, which lacks the 2L protein that has been shown to bind and inhibit the biological activities of multiple human cytokines. TPVK02L/66R is a double knockout TPV, where 2L and 66R (viral thymidine kinase) genes are both deleted. These mutants may potentially enhance the viral tropism toward the cancer cells rather than normal cells. Further engineering of the TPV for the aim of activating the anti-tumor innate immunity was achieved by inserting the bacterial flagellin (FLiC) gene into the viral genome (TPVK066R/2L-FliC). This multi-mechanistic approach may enhance the oncolytic properties of TPV as an oncolytic virus.

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