JX-593: targeted and armed oncolytic and immunotherapeutic poxviruse

[Rich66]

About JX-594
JX-594 is a cancer biotherapeutic product, currently in Phase 2 trials, from a proprietary breakthrough class of targeted and armed oncolytic and immunotherapeutic poxviruses. Tumor destruction and safety was shown in patients with diverse cancer types in three Phase 1 trials; treated patients were end-stage and had no effective therapies available. JX-594 multiplies selectively within cancer cells, leading to their destruction. These newly created copies of JX-594 are then released and are able to infect and eradicate other tumor cells both locally and in distant sites in the body. This cycle of JX-594 replication, cancer cell destruction, release and spread is then repeated. Normal cells are not affected by JX-594 resulting in safety and tolerability. The poxvirus strain backbone of JX-594 has been used safely in millions of people as part of a worldwide vaccination program. This strain naturally targets cancer cells due to common genetic defects in cancer cells. JX-594 was engineered to enhance this natural safety and cancer-selectivity by deleting its thymidine kinase (TK) gene, thus making it dependent on the cellular TK expressed at persistently high levels in cancer cells. To enhance product efficacy, JX-594 is also engineered to express the GM-CSF protein. GM-CSF complements the cancer cell lysis work of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and an anti-tumoral immune attack.



http://www.nature.com/mt/journal/v16...t2008143a.html
Molecular Therapy (2008) 16 9, 1637–1642 doi:10.1038/mt.2008.143
The Targeted Oncolytic Poxvirus JX-594 Demonstrates Antitumoral, Antivascular, and Anti-HBV Activities in Patients With Hepatocellular Carcinoma

Ta-Chiang Liu¹, Taeho Hwang², Byeong-Ho Park³, John Bell¹ and David H Kirn¹

1. ¹JENNEREX Biotherapeutics, San Francisco, California, USA
2. ²Department of Pharmacology, Pusan National University, Busan, South Korea
3. ³Department of Radiology, Dong-A University, Busan, South Korea

Correspondence: David H. Kirn, JENNEREX Biotherapeutics, One Market Street, Spear Tower, Suite 2260, San Francisco, California 94105, USA. E-mail: dkirn@jennerex.com
The first two authors contributed equally to this work.
Received 10 April 2007; Accepted 16 June 2008; Published online 15 July 2008.

Top of pageAbstract

JX-594 is a targeted oncolytic poxvirus that is designed to eradicate cancer cells having cell-cycle defects, through replication, cell lysis, and spread within tumors; oncolysis-induced tumor vascular shutdown and immunostimulation are augmented by granulocyte monocyte–colony-stimulating factor (GM-CSF) transgene expression. We have previously shown, in animal models of hepatocellular carcinoma (HCC), that JX-594 is a promising anticancer agent. We tested JX-594 in three patients with advanced refractory hepatitis B virus (HBV)-associated HCC through intratumoral administration. JX-594 treatment was well-tolerated and resulted in antitumoral efficacy in all three patients, despite the presence of high levels of neutralizing antibodies. JX-594 replication, its release into the circulation, distant tumor targeting were demonstrated. JX-594 administration resulted in the induction of antivascular cytokines, and was associated with tumor vascular shutdown. We also showed, for the first time, that oncolytic virotherapy can suppress underlying HBV replication in HCC patients, and that tumor tissue could be the primary source of acute HBV replication and acute post-treatment HBV release. JX-594 treatment in HBV-associated HCC warrants further clinical testing; a Phase II trial is underway.