title: The emerging therapeutic potential of the oncolytic immunotherapeutic Pexa-Vec (JX-594).
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).
authors: SillaJen Inc, Seoul, South Korea.
authors: Caroline J
authors: CJ
authors: Breitbach
authors: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors: John C
authors: JC
authors: Bell
authors: SillaJen Inc, Seoul, South Korea.
authors: Tae-Ho
authors: TH
authors: Hwang
authors: SillaJen Inc, Seoul, South Korea.
authors: David H
authors: DH
authors: Kirn
authors: SillaJen Inc, Seoul, South Korea.
authors: James
authors: J
authors: Burke
keywords: JX-594; Pexa-Vec; hepatocellular carcinoma; oncolytic immunotherapy