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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Application of Natural Products in Cancer Therapy by Targeting Apoptosis Pathways
Current Drug Metabolism Suppressing Glioblastoma Stem Cell Function by Aldehyde Dehydrogenase Inhibition with Chloramphenicol or Disulfiram as a New Treatment Adjunct: A Hypothesis
Current Stem Cell Research & Therapy Endoplasmic Reticulum and Mitochondria: Independent Roles and Crosstalk in Fatty Liver Diseases and Hepatic Inflammation
Current Pharmaceutical Design Development of Medical Images in Differentiating Benign from Malignant Thyroid Nodules
Current Medical Imaging Protective Effect of Anthocyanins on Radiation-induced Hippocampal Injury through Activation of SIRT3
Current Pharmaceutical Design Multiple Target-Specific Molecular Imaging Agents Detect Liver Cancer in a Preclinical Model
Current Molecular Medicine Transition Metal Based Anticancer Drugs
Current Topics in Medicinal Chemistry 3-Carboranyl Thymidine Analogues (3CTAs) and Other Boronated Nucleosides for Boron Neutron Capture Therapy
Anti-Cancer Agents in Medicinal Chemistry Editorial [Hot Topic: Proteome/Protein/Peptide in Molecular Medicine (Guest Editor: John M. Luk)
Protein & Peptide Letters Ceramide and Apoptosis: Exploring the Enigmatic Connections between Sphingolipid Metabolism and Programmed Cell Death
Anti-Cancer Agents in Medicinal Chemistry Direct Evidence on the Immune-Mediated Spontaneous Regression of Human Cancer: An Incentive for Pharmaceutical Companies to Develop a Novel Anti-Cancer Vaccine
Current Pharmaceutical Design Targeting Receptor Tyrosine Kinase Pathways in Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Cell Cycle Regulatory Kinase Modulators: Interim Progress and Issues
Current Topics in Medicinal Chemistry Tailored Quinolines Demonstrate Flexibility to Exert Antitumor Effects through Varied Mechanisms-A Medicinal Perspective
Anti-Cancer Agents in Medicinal Chemistry Novel Implications for Lysophospholipids, Lysophosphatidic Acid and Sphingosine 1-Phosphate, as Drug Targets in Cancer
Anti-Cancer Agents in Medicinal Chemistry Accuracy of a Topical PET/CT Scanner on SUV Measurements of Small Volumes SUV
Current Medical Imaging LncRNA as a Therapeutic Target for Angiogenesis
Current Topics in Medicinal Chemistry Microtubule-targeting Anticancer Agents from Marine Natural Substance
Anti-Cancer Agents in Medicinal Chemistry Antitumor Effect of Butanoylated Heparin with Low Anticoagulant Activity on Lung Cancer Growth in Mice and Rats
Current Cancer Drug Targets The Role of Pemetrexed Combined with Targeted Agents for Non-Small Cell Lung Cancer
Current Drug Targets