研究人员首次表示，向静脉注射一剂遗传工程病毒就可以定向治疗癌症，杀死患者体内的肿瘤细胞而不伤害健康组织。
多年来，科学家一直着迷于一种想法：用病毒来提醒免疫系统找出并摧毁癌细胞。近几年，随着遗传工程学上的进步，他们得以定制针对肿瘤的病毒。
但是，迄今唯一得到监管机构批准的“溶瘤病毒”在中国，用于治疗头部和颈部的癌症。
在《自然》杂志周三发表的一项研究中，渥太华大学和私营生物技术公司詹纳莱克斯公司（Jennerex）等机构的科学家说，一项对试验性病毒疗法JX-594开展的小规模早期试验发现，它持续作用于肿瘤，副作用极小而且持续时间短。
这种试验性病毒下一步将在肝癌患者身上进行中期测试。
詹纳莱克斯公司首席科学官、渥太华医院研究所的资深科学家约翰·贝尔博士说：“化疗会产生强烈的副作用。接受这种疗法的患者只有24小时的流感症状，然后就一切正常了。”
此次试验的目的是评价JX-594的安全性，试验涉及23名各类晚期癌症患者。
试验还发现，8名得到最高剂量JX-594的患者当中有6名的肿瘤稳定下来或缩小了。
有证据表明，这个组当中，病毒在7名患者(即87%)的肿瘤内复制，但在他们的正常组织中却没有复制。
贝尔博士说，下一步是在120名肝癌患者身上进行病毒疗法试验。
他说，对JX-594的较早试验显示，这种病毒在肝癌中的活性很强。因为某些肝癌由病毒造成(比如乙肝病毒)，那些癌细胞可能对另一种病毒更为敏感。
JX-594取自一种曾经普遍用于给儿童接种预防天花的病毒。(生物谷 Bioon.com）
doi:10.1038/nature10358
PMC:
PMID:
Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans
Caroline J. Breitbach; James Burke; Derek Jonker; Joe Stephenson; Andrew R. Haas; Laura Q. M. Chow; Jorge Nieva; Tae-Ho Hwang; Anne Moon; Richard Patt; Adina Pelusio; Fabrice Le Boeuf; Joe Burns; Laura Evgin; Naomi De Silva; Sara Cvancic; Terri Robertson; Ji-Eun Je; Yeon-Sook Lee; Kelley Parato; Jean-Simon Diallo; Aaron Fenster; Manijeh Daneshmand; John C. Bell; David H. Kirn
The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumour tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for replication, transgene expression and amplification in cancer cells harbouring activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed by cell lysis and anticancer immunity1. Here we show in a clinical trial that JX-594 selectively infects, replicates and expresses transgene products in cancer tissue after intravenous infusion, in a dose-related fashion. Normal tissues were not affected clinically. This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans.
