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Preclinical safety and activity of recombinant VSV‐IFN‐β in an immunocompetent model of squamous cell carcinoma of the head and neck
Author(s) -
Kurisetty Vittal V. S.,
Heiber Joshua,
Myers Rae,
Pereira Guilherme S.,
Goodwin Jarrard W.,
Federspiel Mark J.,
Russell Stephen J.,
Peng Kah Whye,
Barber Glen,
Merchan Jaime R.
Publication year - 2014
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.23502
Subject(s) - vesicular stomatitis virus , in vivo , interferon , in vitro , recombinant dna , head and neck squamous cell carcinoma , medicine , head and neck cancer , cytotoxicity , stomatitis , cancer research , immunology , biology , virus , pathology , cancer , gene , biochemistry , microbiology and biotechnology
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. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1619–1627, 2014