?一种“超级”生物酶Akt1能通过延长枝状细胞的寿命而得到更好的肿瘤疫苗,这些枝状细胞是免疫系统的总开关,可以提升攻击癌症细胞的T细胞。
??BCM的免疫学副教授David Spencer博士表示:“通过延长枝状细胞的生命,我们可以激活并促进期望的免疫反应。在癌症患者中,这种反应就是T细胞的数量增加。枝状细胞生命越长,活跃度越高,就能得到越多的帮助T细胞增加的因子,并最终由T淋巴细胞得到所需要的细胞毒素,杀死癌症细胞。”
??他还说:“枝状细胞是免疫系统的总开关,能决定面对病原体以及肿瘤是采取强烈的免疫反应还是缓和的免疫反应。”利用精巧的实验室技术,Spencer和同事发现Akt1是决定枝状细胞生存的关键因素。然后小组创造了一种能让枝状细胞生存更长,促进免疫反应的Akt1。
??为了实现之一效果,科学家改变了酶结构,使它可以和质膜的特定部分作用,让Akt1有更特定的功能。然后小组还去掉了会引发副作用的Akt1分子结构。Spencer说:“结果表明改变后的分子更加强大。”他的研究生Dongsu Park在创造这种超级Akt1方面做了很多工作。
??利用特定的腺病毒,他和同事将改良后的超级Akt1引入了枝状细胞中。Park说:“像预期的一样,这些枝状细胞更有力,生命更长,不论是在实验室还是小鼠。它去处了小鼠体内很多恶性肿瘤细胞。”小组发现Akt1对人类枝状细胞也有作用。
英文原文:
'Super' enzyme that boosts effect of tumour vaccines
Washington, Dec 4: Researchers at Baylor College of Medicine report that a "super" form of the enzyme Akt1 could provide the key to boosting the effect of tumour vaccines by extending the lives of dendritic cells - the immune-system master switches that promote the response of T-cells, which attack tumours.
"By keeping the dendritic cells alive longer, you extend the window of activation, promoting the desirable immune response, which in the case of cancer, is the expansion of T-cells. The longer your dendritic cells are alive and active, the more likely you are to expand the appropriate T-helper repertoire and ultimately the desirable cytotoxic (cell killing) T-lymphocytes," said David Spencer, associate professor of immunology at BCM.
"The dendritic cells are the master switch in the immune system. They decide whether there will be a robust immune response or a tempered immune response to pathogens or cancer," he said.
Spencer and his colleagues found that Akt1 is essential for dendritic cell survival and so they decided to develop a more potent form of Akt1 that would enable the dendritic cells to live longer, boosting immune response.
To do this, they altered the enzyme so that it targeted a particular domain on the plasma membrane of the cell where signalling occurred, making the action of Akt1 more specific. They then eliminated a small part of the Akt1 molecule that had a negative or inhibitory effect.
"It turned out that the altered molecule was much more potent," Spencer said.
"As predicted, these dendritic cells lived longer and were more potent, both in the laboratory and in mice," he said. "It led to the elimination of some very aggressive tumours in the mice."
In the laboratory, they found that the "super" Akt1 also has a potent effect on human dendritic cells as well, although it has not been used to treat people yet.
The study is published in the current issue of the journal Nature Biotechnology.