Date of Award

6-2014

Degree Name

Doctor of Philosophy

Department

Biological Sciences

First Advisor

Dr. Karim Essani

Second Advisor

Dr. Bruce Bejcek

Third Advisor

Dr. Brian C. Tripp

Fourth Advisor

Dr. Nick Duesbery

Abstract

Cancers of the colon and rectum are a significant cause of morbidity and mortality worldwide and existing therapies often perform poorly for individuals afflicted with advanced stage disease. Oncolytic virotherapy is an emerging therapeutic modality which shows great promise for addressing this serious medical need. Herein we describe the in vivo testing of recombinant variants of the tanapoxvirus (TPV), a virus endemic to equatorial Africa which causes a mild and self-limiting disease in humans. Recombinant tanapoxviruses were made deleted for the 66R gene, the 2L gene, or both. Some of the recombinants were armed with mouse chemotactic protein 1 (mCCL2/mMCP-1), mouse granulocyte-monocyte colony stimulating factor (mGM-CSF), or bacterial flagellin (fliC). Tumors were induced in athymic nude mice by implantation of HCT 116 cells and subsequently treated by a single intratumoral injection with of one of the recombinant TPVs. Significant xenograft regression was seen in tumors treated with virus TPV/Δ2L/Δ66R/fliC, and to a lesser extent the recombinants TPV/Δ2L and TPV/Δ66R. Our results suggest that oncolytic recombinants of the TPV may be effective virotherapeutic agents for colorectal cancers in humans and should be explored further to fully realize their potential.

Access Setting

Dissertation-Open Access

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