title: Oncolytic vesicular stomatitis virus as a treatment for neuroendocrine tumors.
abstract: BACKGROUND
  Therapeutic goals for neuroendocrine tumors (NETs) not amenable to operative cure are limited to relieving symptoms and slowing progression. Many malignancies acquire defective antiviral responses as they undergo unregulated proliferation. Therefore, we explored the abilities of recombinant wild-type vesicular stomatitis virus and an attenuated matrix protein mutant (M51R-VSV) to exploit defective antiviral pathways in NETs.
  
  
  METHODS
  Viral infectivity and lethality were evaluated in a panel of human NET cell lines H727, UMC-11, and CNDT2.5. We evaluated β-interferon pathways in these cells to define the acquired defect. Murine xenografts were treated with a single intratumoral injection of M51R-VSV to study viral efficacy in vivo.
  
  
  RESULTS
  VSV infected >99% of cells within 24 hours and killed >95% within 72 hours. NET cells did not produce relevant amounts of β-interferon after infection, but exogenous β-interferon protected cells from oncolysis. Treatment with M51R-VSV resulted in suppressed tumor growth (mean value ± standard error of the mean) compared with mock-infected xenografts for H727 (87 ± 72% vs. 2,197 ± 335%; P < .001), UMC-11 (13 ± 59% vs. 1,471 ± 324%; P < .001), and CNDT2.5 (81 ± 121% vs. 1,576 ± 349%; P = .001).
  
  
  CONCLUSIONS
  VSV infects and kills human NETs by exploiting their inability to produce a type I antiviral response. Therefore, M51R-VSV is an excellent candidate for the treatment of advanced NETs.
authors: Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, NC.
authors: Reese W
authors: RW
authors: Randle
authors: Scott A
authors: SA
authors: Northrup
authors: S Joseph
authors: SJ
authors: Sirintrapun
authors: Douglas S
authors: DS
authors: Lyles
authors: John H
authors: JH
authors: Stewart
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D018358:Neuroendocrine Tumors / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology; D018116:Vesiculovirus / Q000235:genetics / Q000502:physiology; D014763:Viral Matrix Proteins / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C094460:M protein, Vesicular stomatitis virus; D014763:Viral Matrix Proteins; D016899:Interferon-beta
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