科学家在《自然—医学》杂志上撰文称，他们发现了利用JX-594病毒感染并杀死晚期肝癌患者体内癌细胞的剂量依赖性治疗效果的证据。
JX-594是一种经过修改的牛痘病毒。先前有关该病毒的研究也只是进行了第一期，David Kirn等人首次针对JX-594进行了剂量确定性研究并发现了这种病毒可以诱发抗肿瘤免疫反应的证据。他们发现原发性肝癌患者在注射了高剂量的病毒后，其生命延长时间的中间值可达到14.1个月，而接受低剂量注射的患者只有6.7个月的生命延长期。
虽然以上研究结果无疑给肿瘤治疗新法研究带来希望，但仍需要通过更大规模的安慰剂对照试验确认这项研究结果，JX-594保护功效的有关机制也需要进一步研究确定。（生物谷Bioon.com）
doi:10.1038/nm.3089
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Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer
Jeong Heo, Tony Reid, Leyo Ruo, Caroline J Breitbach, Steven Rose, Mark Bloomston, Mong Cho, Ho Yeong Lim, Hyun Cheol Chung, Chang Won Kim, James Burke, Riccardo Lencioni, Theresa Hickman, Anne Moon, Yeon Sook Lee, Mi Kyeong Kim, Manijeh Daneshmand, Kara Dubois, Lara Longpre, Minhtran Ngo, Cliona Rooney, John C Bell, Byung-Geon Rhee, Richard Patt, Tae-Ho Hwang
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.
