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.

Abstract

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.