近日,，來(lái)自英國(guó)利茲大學(xué)和倫敦癌癥研究所的研究者通過(guò)研究揭示了“搭便車(chē)”病毒（hitch-hiking virus）是如何受到血液中抗體的保護(hù)以及中和抗癌特性的。這項(xiàng)研究建議,，病毒療法應(yīng)該在門(mén)診病人中進(jìn)行,，就像標(biāo)準(zhǔn)的化學(xué)療法因子一樣，使得在治療癌癥上具有潛在的效用,。
呼腸孤病毒可以對(duì)疾病實(shí)施兩次攻擊,，因此成為治療癌癥的一種有效療法。并不僅僅是病毒可以直接殺死癌細(xì)胞,，而且病毒也可以激發(fā)機(jī)體的免疫系統(tǒng),，更有利于機(jī)體清楚殘存的癌細(xì)胞。目前這種病毒療法正在病人中進(jìn)行試驗(yàn),，知道現(xiàn)在醫(yī)生并不能確定這種療法是不是最好的療法,。盡管病毒可以直接被注射入腫瘤細(xì)胞中，這也是一個(gè)相對(duì)復(fù)雜的過(guò)程,，需要精密的技術(shù)操作,。
研究者表示如果通過(guò)靜脈注射，病毒將有可能不會(huì)到達(dá)癌細(xì)胞處,，這將不能達(dá)到殺滅癌細(xì)胞的目的,。通過(guò)靜脈注射將使得血液中抗體會(huì)中和病毒。但是目前在一小部分病人中的試驗(yàn)結(jié)果可知,，情況并不是這樣子的，事實(shí)上,，病毒在通過(guò)血管到達(dá)癌細(xì)胞的時(shí)候依然保持著活性,。研究者Alan表示，呼腸孤病毒看起來(lái)比我們想象中要聰明很多,，病毒可以通過(guò)隱藏自己來(lái)躲避機(jī)體的免疫系統(tǒng),，最終達(dá)到目的地，這將使得病毒療法非常有前景,。
這項(xiàng)研究通過(guò)對(duì)10個(gè)病人進(jìn)行實(shí)驗(yàn)（這些病人患腸癌,，經(jīng)手術(shù)后癌細(xì)胞轉(zhuǎn)移至肝臟），所有病人在手術(shù)之前都給予了每周5個(gè)劑量的病毒量,。隨后經(jīng)過(guò)對(duì)病人血液進(jìn)行檢測(cè),，結(jié)果顯示活性病毒和血細(xì)胞直接相關(guān)。對(duì)病人手術(shù)后,，研究者通過(guò)分析移除的癌組織發(fā)現(xiàn),，活性病毒的確在腫瘤中存在,，而且病毒并不會(huì)在正常的肝臟組織中存在。這就再次證實(shí)了呼腸孤病毒可以通過(guò)靜脈注射進(jìn)入血液,，然后通過(guò)隱藏最終進(jìn)入患處作用,。相關(guān)研究成果刊登在了國(guó)際著名雜志Science Translational Medicine上。（生物谷Bioon.com）
編譯自：'Hitchhiking' Viral Therapy Deals a Double Blow to Cancer
編譯者：天使托
doi:10.1126/scitranslmed.3003578
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PMID:
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.
