Sci Transl Med：呼肠孤病毒可“搭便车”进入患处杀灭癌细胞

近日，来自英国利兹大学和伦敦癌症研究所的研究者通过研究揭示了“搭便车”病毒（hitch-hiking virus）是如何受到血液中抗体的保护以及中和抗癌特性的。这项研究建议，病毒疗法应该在门诊病人中进行，就像标准的化学疗法因子一样，使得在治疗癌症上具有潜在的效用。

呼肠孤病毒可以对疾病实施两次攻击，因此成为治疗癌症的一种有效疗法。并不仅仅是病毒可以直接杀死癌细胞，而且病毒也可以激发机体的免疫系统，更有利于机体清楚残存的癌细胞。目前这种病毒疗法正在病人中进行试验，知道现在医生并不能确定这种疗法是不是最好的疗法。尽管病毒可以直接被注射入肿瘤细胞中，这也是一个相对复杂的过程，需要精密的技术操作。

研究者表示如果通过静脉注射，病毒将有可能不会到达癌细胞处，这将不能达到杀灭癌细胞的目的。通过静脉注射将使得血液中抗体会中和病毒。但是目前在一小部分病人中的试验结果可知，情况并不是这样子的，事实上，病毒在通过血管到达癌细胞的时候依然保持着活性。研究者Alan表示，呼肠孤病毒看起来比我们想象中要聪明很多，病毒可以通过隐藏自己来躲避机体的免疫系统，最终达到目的地，这将使得病毒疗法非常有前景。

这项研究通过对10个病人进行实验（这些病人患肠癌，经手术后癌细胞转移至肝脏），所有病人在手术之前都给予了每周5个剂量的病毒量。随后经过对病人血液进行检测，结果显示活性病毒和血细胞直接相关。对病人手术后，研究者通过分析移除的癌组织发现，活性病毒的确在肿瘤中存在，而且病毒并不会在正常的肝脏组织中存在。这就再次证实了呼肠孤病毒可以通过静脉注射进入血液，然后通过隐藏最终进入患处作用。相关研究成果刊登在了国际著名杂志Science Translational Medicine上。

编译自：'Hitchhiking' Viral Therapy Deals a Double Blow to Cancer

编译者：天使托

doi:10.1126/scitranslmed.3003578
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Cell Carriage, Delivery, and Selective Replication of an Oncolytic Virus in Tumor in Patients

Robert A. Adair1,*, Victoria Roulstone2,*, Karen J. Scott1, Ruth Morgan1, Gerard J. Nuovo3, Martin Fuller4, Deborah Beirne1, Emma J. West1, Victoria A. Jennings1, Ailsa Rose1, Joan Kyula2, Sheila Fraser1, Rajiv Dave1, David A. Anthoney1, Alison Merrick1, Robin Prestwich1, Amer Aldouri1, Oliver Donnelly1, Hardev Pandha5, Matt Coffey6, Peter Selby1, Richard Vile7, Giles Toogood1, Kevin Harrington2,* and Alan A. Melcher1,*,†

Oncolytic viruses, which preferentially lyse cancer cells and stimulate an antitumor immune response, represent a promising approach to the treatment of cancer. However, how they evade the antiviral immune response and their selective delivery to, and replication in, tumor over normal tissue has not been investigated in humans. Here, we treated patients with a single cycle of intravenous reovirus before planned surgery to resect colorectal cancer metastases in the liver. Tracking the viral genome in the circulation showed that reovirus could be detected in plasma and blood mononuclear, granulocyte, and platelet cell compartments after infusion. Despite the presence of neutralizing antibodies before viral infusion in all patients, replication-competent reovirus that retained cytotoxicity was recovered from blood cells but not plasma, suggesting that transport by cells could protect virus for potential delivery to tumors. Analysis of surgical specimens demonstrated greater, preferential expression of reovirus protein in malignant cells compared to either tumor stroma or surrounding normal liver tissue. There was evidence of viral factories within tumor, and recovery of replicating virus from tumor (but not normal liver) was achieved in all four patients from whom fresh tissue was available. Hence, reovirus could be protected from neutralizing antibodies after systemic administration by immune cell carriage, which delivered reovirus to tumor. These findings suggest new preclinical and clinical scheduling and treatment combination strategies to enhance in vivo immune evasion and effective intravenous delivery of oncolytic viruses to patients in vivo.