The targeted oncolytic poxvirus JX-594 demonstrates antitumoral, antivascular, and anti-HBV activities in patients with hepatocellular carcinoma.
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.
Liu
Ta-Chiang
TC
JENNEREX Biotherapeutics, San Francisco, California 94105, USA.
Hwang
Taeho
T
Park
Byeong-Ho
BH
Bell
John
J
Kirn
David H
DH
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000556:secondary / Q000628:therapy*; D018147:Chordopoxvirinae / Q000235:genetics*; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D050130:Oncolytic Virotherapy; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014779:Virus Replication
D016207:Cytokines; D004279:DNA, Viral; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor