title: Oncolytic adenoviruses targeted to Human Papilloma Virus-positive head and neck squamous cell carcinomas.
abstract: OBJECTIVE
  In recent years, the incidence of Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) has markedly increased. Our aim was to design a novel therapeutic agent through the use of conditionally replicative adenoviruses (CRAds) that are targeted to the HPV E6 and E7 oncoproteins.
  
  
  METHODS
  Each adenovirus included small deletion(s) in the E1a region of the genome (Δ24 or CB016) intended to allow for selective replication in HPV-positive cells. In vitro assays were performed to analyze the transduction efficiency of the vectors and the cell viability following viral infection. Then, the UPCI SCC090 cell line (HPV-positive) was used to establish subcutaneous tumors in the flanks of nude mice. The tumors were then treated with either one dose of the virus or four doses (injected every fourth day).
  
  
  RESULTS
  The transduction analysis with luciferase-expressing viruses demonstrated that the 5/3 fiber modification maximized virus infectivity. In vitro, both viruses (5/3Δ24 and 5/3CB016) demonstrated profound oncolytic effects. The 5/3CB016 virus was more selective for HPV-positive HNSCC cells, whereas the 5/3Δ24 virus killed HNSCC cells regardless of HPV status. In vivo, single injections of both viruses demonstrated anti-tumor effects for only a few days following viral inoculation. However, after four viral injections, there was statistically significant reductions in tumor growth when compared to the control group (p<0.05).
  
  
  CONCLUSIONS
  CRAds targeted to HPV-positive HNSCCs demonstrated excellent in vitro and in vivo therapeutic effects, and they have the potential to be clinically translated as a novel treatment modality for this emerging disease.
authors.affiliation: Department of Surgery, University of Minnesota, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: LaRocca
authors.affiliation: Department of Surgery, University of Minnesota, United States.
authors.forename: Joohee
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Surgery, University of Minnesota, United States.
authors.forename: Amanda O
authors.initials: AO
authors.lastname: Salzwedel
authors.affiliation: Department of Surgery, University of Minnesota, United States; Masonic Cancer Center, University of Minnesota, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Davydova
authors.affiliation: Department of Diagnostic & Biological Sciences, School of Dentistry, University of Minnesota, United States.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Herzberg
authors.affiliation: Department of Diagnostic & Biological Sciences, School of Dentistry, University of Minnesota, United States.
authors.forename: Rajaram
authors.initials: R
authors.lastname: Gopalakrishnan
authors.affiliation: Department of Surgery, University of Minnesota, United States; Masonic Cancer Center, University of Minnesota, United States; Institute of Molecular Virology, University of Minnesota, United States. Electronic address: yamam016@umn.edu.
authors.forename: Masato
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D052685:Alphapapillomavirus / Q000472:pathogenicity*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D045744:Cell Line, Tumor; D005822:Genetic Vectors; D006258:Head and Neck Neoplasms / Q000821:virology*; D006801:Humans; D015552:Injections, Intralesional; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D014779:Virus Replication
keywords: Head and neck cancer; Human papillomavirus; Oncolytic adenovirus; Squamous cell carcinoma