Abstract
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.
Keywords: Oncolytic poxvirus, JX-594, Cancer, Oncolytic viruses, vaccinia vaccine strain, granulocytemacrophage colony stimulating factor (GM-CSF), metastatic disease, multiple mechanisms-of-action (MOAs)
Current Pharmaceutical Biotechnology
Title:Targeted and Armed Oncolytic Poxviruses for Cancer: the Lead Example of JX-594
Volume: 13 Issue: 9
Author(s): Caroline J. Breitbach, Steve H. Thorne, John C. Bell and David H. Kirn
Affiliation:
Keywords: Oncolytic poxvirus, JX-594, Cancer, Oncolytic viruses, vaccinia vaccine strain, granulocytemacrophage colony stimulating factor (GM-CSF), metastatic disease, multiple mechanisms-of-action (MOAs)
Abstract: 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.
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Cite this article as:
J. Breitbach Caroline, H. Thorne Steve, C. Bell John and H. Kirn David, Targeted and Armed Oncolytic Poxviruses for Cancer: the Lead Example of JX-594, Current Pharmaceutical Biotechnology 2012; 13 (9) . https://dx.doi.org/10.2174/138920112800958922
DOI https://dx.doi.org/10.2174/138920112800958922 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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