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【bio-news】构建更好的肿瘤杀手
构建更好的肿瘤杀手
By Jocelyn Kaiser
ScienceNOW Daily News
31 August 2006
In a first for gene therapy, researchers have successfully treated cancer patients by genetically modifying their immune cells to attack tumors. Although the treatment worked in only two of 17 patients, the researchers say this proof of concept, reported online today in Science, should pave the way for more gene-therapy cancer cures.
在首次基因治疗中，研究者成功地通过修改肿瘤患者的遗传信息，使他们的免疫细胞攻击肿瘤。虽然这种疗法只对17个患者中的2个起作用，但今日Science在线报道中，研究者称这将为进一步用基因治疗癌症铺平道路。
Steven Rosenberg's group at the National Cancer Institute (NCI) in Bethesda, Maryland, has been working on ways to rev up immune cells to vanquish cancer for 2 decades. A few years ago, the researchers removed tumor-attacking immune cells called T cells from melanoma patients, grew more in the lab, and reinjected them into the patients. The influx of additional tumor-attacking cells pushed the cancer to regress in about half the patients (Science, 25 October 2002, p. 850). But only about half of melanoma victims have these tumor-fighting T cells, and the cells are very scarce in other kinds of cancer.
马里兰州贝塞斯达市的国立癌症研究所（NCI）的Steven Rosenberg研究组已就用这种方法加强免疫细胞击溃肿瘤研究了20年。几年前，研究者从黑素瘤病人身上提取攻击肿瘤称为T细胞的免疫细胞，在实验室体外培养增殖，再将其注回患者。近半数病人因为额外注射的肿瘤攻击细胞病情有了好转(Science, 25 October 2002, p. 850)。但只有一半的黑素瘤患者有这种对抗肿瘤的T细胞，而这种细胞在其他种类的癌症患者中也非常缺乏。
So for 17 patients with advanced melanoma who didn't have tumor-fighting T cells and had failed existing treatments, Rosenberg's team tried gene therapy. The researchers removed normal T cells from the patients' blood, then gave them a powerful guidance system: a molecule that sticks out from the T cell and homes in on melanoma tumor cells. The gene that codes for this molecule was ferried into the cells via a harmless retrovirus. The researchers then injected these modified cells back into the patients.
所以对于那17个缺乏对抗肿瘤的T细胞，而现有的治疗方法也不起作用的晚期黑素瘤患者，Rosenberg的团队尝试了基因疗法。研究者从病人的血液中分离普通T细胞，然后给他们一个有效的制导系统：由T细胞释放的一种分子，定位于黑素瘤细胞。通过无害的逆转录病毒将编码这个分子的基因转运到细胞。研究人员再将这些重新构建的细胞注回病人体内。
In 15 of the patients, the injected cells thrived and made up at least 10% of their total T cells weeks later. Two men who had even higher levels of the modified T cells experienced a dramatic recovery. In one, a liver and armpit tumor that had developed from spreading melanoma cells shrank, and in the other a lung tumor disappeared. Both men remain healthy 18 months after treatment.
病人中的15个，注射的细胞茁壮成长，几周后就至少占到病人总T细胞的10%。而2个有更高比例的修饰T细胞的病人发生了戏剧性的恢复。其中一个患者源于黑素瘤细胞扩散发展而成的肝脏肿瘤缩小，而另一个病人肺部的肿瘤消失。两人都在治疗后保持了18个月的健康。
That success rate is low, Rosenberg admits, but he adds, "this is just a start." Rosenberg's group is now working on a half-dozen ways to improve the treatment, including adding molecules that are better at finding cancers. The team is also hoping to test T cells modified to attack breast, lung, and colon tumors.
Rosenberg承认成功率比较低，但他补充说，“这只是一个开始。” Rosenberg的团队正努力用六种方法改进治疗方案，包括增加能更好发现肿瘤的分子。他们也希望试验修饰T细胞攻击乳腺癌、肺癌、结肠癌。
"The technology will get better," agrees cancer gene therapy researcher Carl June of the University of Pennsylvania. One important result is that the treatment didn't seem to cause a serious autoimmune response as a side effect, he adds. "I'm very happy to see this," he says. "This shows the basic safety. That's really good news for the field."
“这项技术将变得更好，” 宾夕法尼亚大学癌症基因治疗研究员Carl June赞同。一个重要的结论是这项治疗看上去不会造成严重的自身免疫的副作用，他补充说，“我很高兴看见这项成果，它显示了基本的安全，这对于这个领域真是个好消息。”
Shrinkage.
A liver tumor (dark gray) practically disappears thanks to modified T cells.
Credit: R. A. MORGAN ET AL., SCIENCE
多亏修饰T细胞，一个肝部肿瘤（深灰色）几乎消失。
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作者:admin@医学,生命科学 2011-09-02 17:13
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