Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Pharmacology and Toxicology, MS
States, J. Christopher
Viruses--Therapeutic use; Lungs--Cancer--Treatment
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.
Wechman, Stephen, "Improved oncolytic virotherapy by increasing virus spread within tumors." (2015). Electronic Theses and Dissertations. Paper 2208.