Targeted and armed oncolytic poxviruses for cancer: the lead example of JX-594

Oncolytic viruses (OVs) are designed to replicate in, and subsequently lyse cancer cells. Numerous oncolytic virus platforms are currently in development. Here we review preclinical and clinical experience with JX-594, the lead candidate from the targeted and armed oncolytic poxvirus class. JX-594 i...

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Bibliographic Details
Published inCurrent pharmaceutical biotechnology Vol. 13; no. 9; p. 1768
Main Authors Breitbach, Caroline J, Thorne, Steve H, Bell, John C, Kirn, David H
Format Journal Article
LanguageEnglish
Published Netherlands 01.07.2012
Subjects
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Drug Evaluation, Preclinical
Humans
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - therapy
Neoplasms - virology
Oncolytic Virotherapy - methods
Oncolytic Viruses - genetics
Oncolytic Viruses - metabolism
Oncolytic Viruses - physiology
Poxviridae - genetics
Poxviridae - metabolism
Poxviridae - physiology
Vaccinia virus - genetics
Vaccinia virus - metabolism
Vaccinia virus - physiology
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Summary:Oncolytic viruses (OVs) are designed to replicate in, and subsequently lyse cancer cells. Numerous oncolytic virus platforms are currently in development. Here we review preclinical and clinical experience with JX-594, the lead candidate from the targeted and armed oncolytic poxvirus class. JX-594 is derived from a vaccinia vaccine strain that has been engineered for 1) enhanced cancer targeting and 2) has been "armed" with the therapeutic transgene granulocytemacrophage colony stimulating factor (GM-CSF) to stimulate anti-tumoral immunity. Poxviruses have many ideal features for use as oncolytic agents. The development of oncolytic vaccinia viruses is supported by a large safety database accumulated in the smallpox eradication program. In addition, poxviruses have evolved unique capabilities for systemic spread through the blood that can be harnessed for the treatment of metastatic disease. JX-594 demonstrates a high degree of cancer selectivity and systemic efficacy by multiple mechanisms-of-action (MOAs) in preclinical testing. Data from Phase 1 and 2 clinical trials has confirmed that these features result in potent and systemic efficacy in patients with treatment refractory metastatic cancers.
ISSN:1873-4316
DOI:10.2174/138920112800958922