Date on Master's Thesis/Doctoral Dissertation

8-2015

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

McMasters, Kelly

Committee Co-Chair (if applicable)

Zhou, Heshan

Committee Member

Zhou, Heshan

Committee Member

States, J. Christopher

Committee Member

Myers, Steven

Committee Member

Palmer, Kenneth

Subject

Viruses--Therapeutic use; Lungs--Cancer--Treatment

Abstract

Oncolytic adenoviruses (Ads) have great therapeutic potential for lung cancer. Cancer selective E1b-deleted Ads are safe, however their efficacy remains limited clinically. To improve E1b-deleted Ads, Adhz60 was selected for greater anti-cancer efficacy by a process called bioselection, producing AdUV. AdUV preferentially lysed A549 and H1299 lung cancer cells more effectively than both the cancer selective Adhz60 and non-selective Ad5. AdUV induced greater LC3-II expression, relative to LC3-I, indicating that AdUV (30.9-fold) induced autophagy more effectively than Ad5 (12.2-fold) and Adhz60 (7.8-fold) in A549 cells. Mice treated with AdUV had significantly smaller tumors (p-value < 0.001) and prolonged survival (p-value = 0.0005) than mice treated with the negative control AdGFP. These results suggest that AdUV efficiently lyses lung cancer cells in vitro and in vivo.

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