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Viruses 2016, 8(6), 167; doi:10.3390/v8060167

Development of an Oncolytic Adenovirus with Enhanced Spread Ability through Repeated UV Irradiation and Cancer Selection

1
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA
2
Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA
3
James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA
4
Department of Surgery, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
5
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Joanna Parish
Received: 10 March 2016 / Revised: 17 May 2016 / Accepted: 1 June 2016 / Published: 14 June 2016
(This article belongs to the Section Animal Viruses)
View Full-Text   |   Download PDF [27152 KB, uploaded 14 June 2016]   |  

Abstract

Oncolytic adenoviruses (Ads) have been shown to be safe and have great potential for the treatment of solid tumors. However, the therapeutic efficacy of Ads is antagonized by limited spread within solid tumors. To develop Ads with enhanced spread, viral particles of an E1-wildtype Ad5 dl309 was repeatedly treated with UV type C irradiation and selected for the efficient replication and release from cancer cells. After 72 cycles of treatment and cancer selection, AdUV was isolated. This vector has displayed many favorable characteristics for oncolytic therapy. AdUV was shown to lyse cancer cells more effectively than both E1-deleted and E1-wildtype Ads. This enhanced cancer cell lysis appeared to be related to increased AdUV replication in and release from infected cancer cells. AdUV-treated A549 cells displayed greater expression of the autophagy marker LC3-II during oncolysis and formed larger viral plaques upon cancer cell monolayers, indicating increased virus spread among cancer cells. This study indicates the potential of this approach of irradiation of entire viral particles for the development of oncolytic viruses with designated therapeutic properties. View Full-Text
Keywords: lung cancer; adenovirus; E1b; autophagy; spread; oncolysis lung cancer; adenovirus; E1b; autophagy; spread; oncolysis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wechman, S.L.; Rao, X.-M.; Cheng, P.-H.; Gomez-Gutierrez, J.G.; McMasters, K.M.; Zhou, H.S. Development of an Oncolytic Adenovirus with Enhanced Spread Ability through Repeated UV Irradiation and Cancer Selection. Viruses 2016, 8, 167.

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