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The emerging therapeutic potential of the oncolytic immunotherapeutic Pexa-Vec (JX-594)

Authors Breitbach C, Bell JC, Hwang T, Kirn D, Burke J

Received 30 April 2014

Accepted for publication 15 July 2014

Published 28 January 2015 Volume 2015:4 Pages 25—31


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Caroline J Breitbach,1 John C Bell,2,3 Tae-Ho Hwang,1 David H Kirn,1 James Burke1

1SillaJen Inc, Seoul, South Korea; 2Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada; 3Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada

Abstract: Oncolytic immunotherapeutics (OIs) are viruses designed to preferentially replicate in and lyse cancer cells, thereby triggering antitumor immunity. Numerous oncolytic platforms are currently in clinical development. Here we review preclinical and clinical experience with Pexa-Vec (pexastimogene devacirepvec, JX-594). Pexa-Vec is derived from a vaccinia vaccine strain that has been engineered to target cancer cells and express the therapeutic transgene granulocyte macrophage colony-stimulating factor (GM-CSF) in order to stimulate antitumor immunity. Key to its ability to target metastatic disease is the evolution of unique vaccinia virus characteristics that allow for effective systemic dissemination. Multiple mechanisms of action (MOA) for Pexa-Vec have been demonstrated in preclinical models and patients: 1) tumor cell infection and lysis, 2) antitumor immune response induction, and 3) tumor vascular disruption. This review will summarize data on the Pexa-Vec MOA as well as provide an overview of the Pexa-Vec clinical development program from multiple Phase I studies, Phase II studies in renal cell cancer and colorectal cancer, through Phase IIb clinical testing in patients with advanced hepatocellular carcinoma (primary liver cancer).

Keywords: Pexa-Vec, JX-594, oncolytic immunotherapy, hepatocellular carcinoma

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