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Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer.

Title
 Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer.
Authors
 Jeong Heo; Tony Reid; David H Kirn; Tae-Ho Hwang; Richard Patt; Byung-Geon Rhee; John C Bell; Cliona Rooney; Minhtran Ngo; Lara Longpre; Kara Dubois; Manijeh Daneshmand; Mi Kyeong Kim; Yeon Sook Lee; Anne Moon; Theresa Hickman; Riccardo Lencioni; James Burke; Chang Won Kim; Hyun Cheol Chung; Ho Yeong Lim; Mong Cho; Mark Bloomston; Steven Rose; Caroline J Breitbach; Leyo Ruo
Issue Date
2013
Journal Title
 Nature Medicine
ISSN
 1078-8956
Citation
 Nature Medicine, Vol.19(3) : 329~336, 2013
Abstract
Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear. JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus. To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n=30). Radiologists infused low- or high-dose JX-594 into liver tumors (days 1, 15 and 29); infusions resulted in acute detectable intravascular JX-594 genomes. Objective intrahepatic Modified Response Evaluation Criteria in Solid Tumors (mRECIST) (15%) and Choi (62%) response rates and intrahepatic disease control (50%) were equivalent in injected and distant noninjected tumors at both doses. JX-594 replication and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression preceded the induction of anticancer immunity. In contrast to tumor response rate and immune endpoints, subject survival duration was significantly related to dose (median survival of 14.1 months compared to 6.7 months on the high and low dose, respectively; hazard ratio 0.39; P=0.020). JX-594 demonstrated oncolytic and immunotherapy MOA, tumor responses and dose-related survival in individuals with HCC.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/86497
DOI
10.1038/nm.3089
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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Link
 http://www.nature.com/nm/journal/v19/n3/full/nm.3089.html
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