title: Preclinical safety and activity of recombinant VSV-IFN-β in an immunocompetent model of squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  Recombinant vesicular stomatitis virus expressing interferon-β (VSV-IFN-β) has demonstrated antitumor activity in vitro and in vivo. In preparation for clinical testing in human squamous cell carcinoma (SCC) of the head and neck, we conducted preclinical studies of VSV-IFN-β in syngeneic SCC models.
  
  
  METHODS
  In vitro, VSV-IFN-β (expressing rat or mouse interferon [IFN]-β)-induced cytotoxicity and propagated in rat (FAT-7) or mouse (SCC-VII) SCC cells during normoxia and hypoxia. In vivo, intratumoral administration of VSV-rat-IFN-β or VSV-human-IFN-β in FAT-7 bearing or non-tumor bearing immunocompetent rats did not result in acute organ toxicity or death.
  
  
  RESULTS
  VSV-r-IFN-β replicated predominantly in tumors and a dose dependent anti-VSV antibody response was observed. Intratumoral or intravenous administration of VSV-IFN-β resulted in growth delay and improved survival compared with controls.
  
  
  CONCLUSIONS
  The above data confirm safety and feasibility of VSV-IFN-β administration in immunocompetent animals and support its clinical evaluation in advanced human head and neck cancer.
authors.affiliation: Division of Hematology and Oncology, University of Miami/Miller School of Medicine, Miami, Florida.
authors.forename: Vittal V S
authors.initials: VV
authors.lastname: Kurisetty
authors.forename: Joshua
authors.initials: J
authors.lastname: Heiber
authors.forename: Rae
authors.initials: R
authors.lastname: Myers
authors.forename: Guilherme S
authors.initials: GS
authors.lastname: Pereira
authors.forename: Jarrard W
authors.initials: JW
authors.lastname: Goodwin
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Federspiel
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.forename: Kah Whye
authors.initials: KW
authors.lastname: Peng
authors.forename: Glen
authors.initials: G
authors.lastname: Barber
authors.forename: Jaime R
authors.initials: JR
authors.lastname: Merchan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005240:Feasibility Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007121:Immunocompetence; D016899:Interferon-beta / Q000494:pharmacology*; D053208:Kaplan-Meier Estimate; D051379:Mice; D050130:Oncolytic Virotherapy / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012449:Safety; D018709:Statistics, Nonparametric; D014185:Transplantation, Isogeneic; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D054243:Vesicular Stomatitis / Q000821:virology; D018116:Vesiculovirus / Q000302:isolation & purification*
chemical_list: D016899:Interferon-beta
keywords: biodistribution; preclinical studies; squamous cell carcinoma; syngeneic models; vesicular stomatitis virus