Preclinical safety and activity of recombinant VSV‐IFN‐β in an immunocompetent model of squamous cell carcinoma of the head and neck. Issue 11 (1st February 2014)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Head & neck. Volume 36:Issue 11(2014:Nov.)
• Page Start: 1619
• Page End: 1627
• Publication Date: 2014-02-01
• Subjects: Head -- Diseases -- Periodicals; Neck -- Diseases -- Periodicals; Head -- Periodicals; Neck -- Periodicals; Face -- Periodicals; 617.51059
• DOI: 10.1002/hed.23502
• Languages: English
• ISSNs: 1043-3074

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="hed23502-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="hed23502-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="hed23502-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="hed23502-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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. <italic>Head Neck</italic> 36: 1619–1627, 2014</p> </sec> </abstract>