科學(xué)家在《自然—醫(yī)學(xué)》雜志上撰文稱,，他們發(fā)現(xiàn)了利用JX-594病毒感染并殺死晚期肝癌患者體內(nèi)癌細(xì)胞的劑量依賴性治療效果的證據(jù)。
JX-594是一種經(jīng)過修改的牛痘病毒,。先前有關(guān)該病毒的研究也只是進(jìn)行了第一期,，David Kirn等人首次針對JX-594進(jìn)行了劑量確定性研究并發(fā)現(xiàn)了這種病毒可以誘發(fā)抗腫瘤免疫反應(yīng)的證據(jù)。他們發(fā)現(xiàn)原發(fā)性肝癌患者在注射了高劑量的病毒后,，其生命延長時間的中間值可達(dá)到14.1個月,，而接受低劑量注射的患者只有6.7個月的生命延長期。
雖然以上研究結(jié)果無疑給腫瘤治療新法研究帶來希望,，但仍需要通過更大規(guī)模的安慰劑對照試驗(yàn)確認(rèn)這項(xiàng)研究結(jié)果,，JX-594保護(hù)功效的有關(guān)機(jī)制也需要進(jìn)一步研究確定。（生物谷Bioon.com）
doi:10.1038/nm.3089
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PMID:
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.
