title: Efficacy of systemically administered mutant vesicular stomatitis virus (VSVDelta51) combined with radiation for nasopharyngeal carcinoma.
abstract: OBJECTIVE
  Nasopharyngeal carcinoma (NPC) is a malignancy of the head and neck region that is associated with EBV latency. Curative treatments for NPC achieve modest survival rates, underscoring a need to develop novel therapies. We evaluated the therapeutic potential of a mutant vesicular stomatitis virus (VSVDelta51) as single treatment modality or in combination with ionizing radiation (RT) in NPC.
  
  
  METHODS
  MTS assay was used to assess cell viability in vitro; apoptosis was measured using propidium iodide staining and caspase activation. In vivo experiments were conducted using tumor-bearing nude mice with or without local RT (4 Gy). Apoptosis was assessed in excised tumor sections with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining.
  
  
  RESULTS
  Our data showed that NPC cells are exquisitely sensitive to VSVDelta51 oncolysis, which correlated with the presence of EBV. Efficacy of VSVDelta51 against NPC cells was further augmented when combined with RT. A single systemic injection of VSVDelta51 achieved 50% survival in treated mice, which increased to 83% when combined with local tumor RT. In addition to induction of apoptosis, an antiangiogenic effect of VSVDelta51 was observed in vivo, suggesting a novel tumoricidal mechanism for VSVDelta51. This virus also prevented growth of NPC sphere-forming cells in vitro, showing potential utility in targeting NPC-initiating cells.
  
  
  CONCLUSIONS
  Our data represent the first report showing that EBV-positive NPC cells are exquisitely sensitive to VSVDelta51 oncolysis and documenting the successful utilization of this combinatorial regimen as a novel curative therapeutic strategy for NPC.
authors.affiliation: Division of Applied Molecular Oncology, Ontario Cancer Institute, Toronto, Ontario, Canada.
authors.forename: Nehad M
authors.initials: NM
authors.lastname: Alajez
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Mocanu
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Marie C
authors.initials: MC
authors.lastname: Chia
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Breitbach
authors.forename: Angela B Y
authors.initials: AB
authors.lastname: Hui
authors.forename: Shane
authors.initials: S
authors.lastname: Knowles
authors.forename: John C
authors.initials: JC
authors.lastname: Bell
authors.forename: Pierre
authors.initials: P
authors.lastname: Busson
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takada
authors.forename: Kwok-Wai
authors.initials: KW
authors.lastname: Lo
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: Pat
authors.initials: P
authors.lastname: Gullane
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000532:radiotherapy / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003131:Combined Modality Therapy / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D009368:Neoplasm Transplantation; D016896:Treatment Outcome; D018116:Vesiculovirus / Q000235:genetics / Q000378:metabolism*