?一種“超級(jí)”生物酶Akt1能通過延長枝狀細(xì)胞的壽命而得到更好的腫瘤疫苗,，這些枝狀細(xì)胞是免疫系統(tǒng)的總開關(guān),，可以提升攻擊癌癥細(xì)胞的T細(xì)胞。
??BCM的免疫學(xué)副教授David Spencer博士表示：“通過延長枝狀細(xì)胞的生命,，我們可以激活并促進(jìn)期望的免疫反應(yīng),。在癌癥患者中，這種反應(yīng)就是T細(xì)胞的數(shù)量增加,。枝狀細(xì)胞生命越長,，活躍度越高，就能得到越多的幫助T細(xì)胞增加的因子,，并最終由T淋巴細(xì)胞得到所需要的細(xì)胞毒素,，殺死癌癥細(xì)胞。”
??他還說：“枝狀細(xì)胞是免疫系統(tǒng)的總開關(guān),，能決定面對(duì)病原體以及腫瘤是采取強(qiáng)烈的免疫反應(yīng)還是緩和的免疫反應(yīng),。”利用精巧的實(shí)驗(yàn)室技術(shù)，Spencer和同事發(fā)現(xiàn)Akt1是決定枝狀細(xì)胞生存的關(guān)鍵因素,。然后小組創(chuàng)造了一種能讓枝狀細(xì)胞生存更長,，促進(jìn)免疫反應(yīng)的Akt1。
??為了實(shí)現(xiàn)之一效果,，科學(xué)家改變了酶結(jié)構(gòu),，使它可以和質(zhì)膜的特定部分作用，讓Akt1有更特定的功能,。然后小組還去掉了會(huì)引發(fā)副作用的Akt1分子結(jié)構(gòu),。Spencer說：“結(jié)果表明改變后的分子更加強(qiáng)大。”他的研究生Dongsu Park在創(chuàng)造這種超級(jí)Akt1方面做了很多工作,。
??利用特定的腺病毒,，他和同事將改良后的超級(jí)Akt1引入了枝狀細(xì)胞中。Park說：“像預(yù)期的一樣,，這些枝狀細(xì)胞更有力,，生命更長，不論是在實(shí)驗(yàn)室還是小鼠,。它去處了小鼠體內(nèi)很多惡性腫瘤細(xì)胞,。”小組發(fā)現(xiàn)Akt1對(duì)人類枝狀細(xì)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.
