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
-
Cell Cycle Regulatory Kinase Modulators: Interim Progress and Issues
Current Topics in Medicinal Chemistry Update on the Rheumatologic Manifestations of Malignancy
Current Cancer Therapy Reviews ErbB Targeted Drugs and Angiogenesis
Current Vascular Pharmacology The Role of Androgen Under Normal and Pathological Conditions in Sebaceous Glands: The Possibility of Target Therapy
Current Molecular Pharmacology Duloxetine in the Treatment of Depression: An Overview
Central Nervous System Agents in Medicinal Chemistry Aldose Reductase Enzyme and its Implication to Major Health Problems of the 21st Century
Current Medicinal Chemistry Trans-Platinum Complexes as Anticancer Drugs: Recent Developments and Future Prospects
Current Medicinal Chemistry Editorial [Hot Topic: Reprogramming of Normal and Cancer Stem Cells (Guest Editor: Pier Mario Biava)]
Current Pharmaceutical Biotechnology Does Global Gene Expression Analysis in Type 2 Diabetes Provide an Opportunity to Identify Highly Promising Drug Targets?
Endocrine, Metabolic & Immune Disorders - Drug Targets Synthesis and Biological Evaluation of New Pyrazole-based Thiazolyl Hydrazone Derivatives as Potential Anticancer Agents
Letters in Drug Design & Discovery Small Molecules with EGFR-TK Inhibitor Activity
Current Drug Targets Targeting Proliferating Cell Nuclear Antigen (PCNA) as an Effective Strategy to Inhibit Tumor Cell Proliferation
Current Cancer Drug Targets The Blood-Brain Barrier in Multiple Sclerosis: microRNAs as Key Regulators
CNS & Neurological Disorders - Drug Targets Synthesis and Evaluation of Novel Erucin Analogues as Potential Antitumor Compounds
Letters in Organic Chemistry The Insulin-like Growth Factor-1 Axis and its Potential as a Therapeutic Target in Central Nervous System (CNS) Disorders
Central Nervous System Agents in Medicinal Chemistry “Smart” Nanocarriers: A New Paradigm for Tumor Targeting Drug Delivery Systems
Drug Delivery Letters The Imaging of Apoptosis with the Radiolabelled Annexin A5: A New Tool in Translational Research
Current Clinical Pharmacology Meet the Editorial Board:
Protein & Peptide Letters Diverse Mechanisms of AKT Pathway Activation in Human Malignancy
Current Cancer Drug Targets Polymorphisms of Genes Encoding Phase I Enzymes in Mexican Americans – An Ethnic Comparison Study
Current Pharmacogenomics