JX-594, is engineered based on the vaccinia virus strain and is genetically modified by deleting its thymidine kinase gene to enhance cancer-selectivity. In addition, it has been joined to with GM-CSF gene to stimulate systemic anti-tumoral immune response in the context of product replication and lysis of the infected cancer cells. In a recent pashe I trial, presented at the American Society of Gene Therapy (ASGT) Annual Meeting in
Boston, Massachusetts in June 2008, JX-594 demonstrated that the product was well-tolerated and resulted in clear anti-cancer efficacy in patients with liver cancer. Three patients with advanced treatment-refractory hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) were treated with JX-594. Objective radiographic responses were demonstrated. Serum tumor markers, which correlate with tumor burden over time in patients, decreased by up to 95 percent after treatment. JX-594 replication, its release into the circulation and distant tumor targeting and infection were demonstrated.
Another study that was presented reported 14 patients with a variety of treatment-refractory cancer types (e.g. liver, colon, lung) in the liver were treated every three weeks with JX-594 by ultrasound-guided intratumoral injection. Patients had advanced cancers that had failed all available therapies and were therefore considered terminal. Responses were reproted.
This is clearly a promising therapy but more research is needed before it can be widely adopted.
J. H. Kim etal, Systemic Armed Oncolytic and Immunologic Therapy for Cancer with JX-594, a Targeted Poxvirus Expressing GM-CSF Molecular Therapy (2006) 14, 361–370
B. Park, T. Hwang, T. Liu, D. Sze, J. Kim, H. Kwon, S. Oh, S. Han, J. Yoon, S. Hong
Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial The Lancet Oncology, Volume 9, Issue 6, Pages 533-542