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- 조회798
Molecular Therapy, Volume 16, Issue 9, September 2008, Pages 1637-1642 | https://doi.org/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 Bell1and David H Kirn1
1JENNEREX Biotherapeutics, San Francisco, California, USA; 2Department of Pharmacology, Pusan National University, Busan, South Korea; 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.
The first two authors contributed equally to this work.
Correspondence: David H Kirn, JENNEREX Biotherapeutics, One Market Street, Spear Tower, Suite 2260, San Francisco, California 94105, USA.
The first two authors contributed equally to this work.
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.
논문정보
- Research article
- 2008년 09월 (BRIC 등록일 2017-12-20)
- 국내+국외 연구진
- 120회 이상 인용된 논문
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