Preclinical safety and activity of recombinant VSV-IFN-β in an immunocompetent model of squamous cell carcinoma of the head and neck

Vittal V S Kurisetty, Joshua Heiber, Rae Myers, Guilherme S. Pereira, W. Jarrard Goodwin, Mark J. Federspiel, Stephen J. Russell, Kah W hye Peng, Glen N Barber, Jaime R Merchan

Research output: Contribution to journalArticle

12 Scopus citations

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.

CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)1619-1627
Number of pages9
JournalHead and Neck
Volume36
Issue number11
DOIs
StatePublished - Nov 1 2014

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Keywords

  • biodistribution
  • preclinical studies
  • squamous cell carcinoma
  • syngeneic models
  • vesicular stomatitis virus

ASJC Scopus subject areas

  • Medicine(all)

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