Development of an Oncolytic Adenovirus with Enhanced Spread Ability through Repeated UV Irradiation and Cancer Selection.
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.
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. slwech01@louisville.edu.|Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA. slwech01@louisville.edu.
Stephen L
SL
Wechman
James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA. x0rao001@louisville.edu.
Xiao-Mei
XM
Rao
Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. paisin.paisin@gmail.com.
Pei-Hsin
PH
Cheng
Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA. jgguti01@louisville.edu.|James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA. jgguti01@louisville.edu.
Jorge G
JG
Gomez-Gutierrez
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. mcmasters@louisville.edu.|Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA. mcmasters@louisville.edu.|James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA. mcmasters@louisville.edu.
Kelly M
KM
McMasters
Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA. hszhou01@louisville.edu.|James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA. hszhou01@louisville.edu.|Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA. hszhou01@louisville.edu.
H Sam
HS
Zhou
D000256:Adenoviridae / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification* / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D050504:Oncolytic Viruses / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification* / Q000528:radiation effects; D012692:Serial Passage; D014466:Ultraviolet Rays; D010948:Viral Plaque Assay
E1b; adenovirus; autophagy; lung cancer; oncolysis; spread