Viral genes were deleted in order to restrict virus replication to cancer cells (deletions in the viral thymidine kinase (TK) and vaccinia growth factor (VGF) ). Without thymidine kinase, the virus cannot replicate and cause damage in normal, healthy tissue. The resulting virus infects cancer cells while leaving healthy cells alone.
In addition, the researchers also spliced a gene (human GM-CSF) into the virus that makes it produce granulocyte-macrophage colony-stimulating factor (GM-CSF), which induces the body’s own immune system to recognize and attack tumor cells by releasing white blood cells. After the virus has destroyed most of the tumors, it stimulates an elevated immune system response, that will mop up remaining cancer cells.
Beginning in July 2006 researchers started treating 13 patients with advanced liver cancer by administering the JX-594 virus directly into the subjects' tumours every three weeks. According to Kirn, the patients entering this trial had a poor prognosis – all previous therapies had failed, and they had an expected survival of only three to four months. He says that the JX-594 treatment seemed to slow the progression of the disease in this small group of patients: seven of the participants survived for more than eight months, of whom three are still alive today, over 15 months later
In a newly published paper appearing in the Journal Clinical Investigation, another modified vaccinia virus called JX-963 was developed, which is a nearly identical virus to JX-594, and reduced liver tumour growth in rabbits. More than 80% of the animals treated with the JX-963 showed a greater than 50% reduction in tumour size. Based on the positive results from the preliminary clinical trial and recent animal experiments, Kirn says his team will conduct phase II trials to see whether the JX-594 virus can help treat other types of tumours, such as head and neck cancers. Human trials are expected to begin early next year.
Journal reference: Journal of Clinical Investigation: Rational strain selection and engineering creates a broad-spectrum, systemically effective oncolytic poxvirus, JX-963 (http://content.the-jci.org/articles/view/32727)
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