研究人員首次表示,，向靜脈注射一劑遺傳工程病毒就可以定向治療癌癥，殺死患者體內(nèi)的腫瘤細(xì)胞而不傷害健康組織,。
多年來,，科學(xué)家一直著迷于一種想法：用病毒來提醒免疫系統(tǒng)找出并摧毀癌細(xì)胞。近幾年,，隨著遺傳工程學(xué)上的進(jìn)步,，他們得以定制針對腫瘤的病毒。
但是,，迄今唯一得到監(jiān)管機(jī)構(gòu)批準(zhǔn)的“溶瘤病毒”在中國,，用于治療頭部和頸部的癌癥。
在《自然》雜志周三發(fā)表的一項(xiàng)研究中,，渥太華大學(xué)和私營生物技術(shù)公司詹納萊克斯公司（Jennerex）等機(jī)構(gòu)的科學(xué)家說,，一項(xiàng)對試驗(yàn)性病毒療法JX-594開展的小規(guī)模早期試驗(yàn)發(fā)現(xiàn),，它持續(xù)作用于腫瘤，副作用極小而且持續(xù)時間短,。
這種試驗(yàn)性病毒下一步將在肝癌患者身上進(jìn)行中期測試,。
詹納萊克斯公司首席科學(xué)官、渥太華醫(yī)院研究所的資深科學(xué)家約翰·貝爾博士說：“化療會產(chǎn)生強(qiáng)烈的副作用,。接受這種療法的患者只有24小時的流感癥狀,，然后就一切正常了。”
此次試驗(yàn)的目的是評價JX-594的安全性,，試驗(yàn)涉及23名各類晚期癌癥患者,。
試驗(yàn)還發(fā)現(xiàn)，8名得到最高劑量JX-594的患者當(dāng)中有6名的腫瘤穩(wěn)定下來或縮小了,。
有證據(jù)表明,，這個組當(dāng)中，病毒在7名患者(即87%)的腫瘤內(nèi)復(fù)制,，但在他們的正常組織中卻沒有復(fù)制,。
貝爾博士說，下一步是在120名肝癌患者身上進(jìn)行病毒療法試驗(yàn),。
他說,，對JX-594的較早試驗(yàn)顯示，這種病毒在肝癌中的活性很強(qiáng),。因?yàn)槟承└伟┯刹《驹斐?比如乙肝病毒),，那些癌細(xì)胞可能對另一種病毒更為敏感。
JX-594取自一種曾經(jīng)普遍用于給兒童接種預(yù)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.
