據(jù)12月21日醫(yī)療快線報道,，愛爾蘭都柏林三一學院的科學家開發(fā)出一種新的疫苗用于在臨床前階段治療癌癥,。研究組由都柏林三一學院實驗免疫學教授Kingston Mills領導，他們發(fā)現(xiàn)了一種新的方法來治療疾病，這種新方法基于調控機體對惡性腫瘤的免疫反應,。這一發(fā)現(xiàn)已申請專利,，并且計劃開發(fā)出疫苗供癌癥患者臨床使用。
第一種疫苗Sipuleucel-T（Provenge）于去年通過許可用于對激素治療無效的前列腺癌患者,。不幸的是,，這種基于細胞的疫苗僅提高了患者平均4.1個月的生存率。疫苗對感染性疾病產生了非常有效免疫反應,，阻止了細菌或病毒的感染。免疫系統(tǒng)同樣也能保護機體對抗腫瘤,，理論上疫苗方法應該對癌癥有效,。在實際中，這已被證明是非常難的,，因為腫瘤不像感染性疾病,，它是起源于正常的人體細胞，并不是由外源物質或能夠觸發(fā)免疫反應的抗原組成,。相反腫瘤細胞產生了能抑制免疫系統(tǒng)功效的分子,。他們產生調節(jié)性細胞抑制了能潛在清除腫瘤的免疫反應。
Mills教授研究小組已經開發(fā)了一種能克服這些障礙的新型疫苗以及免疫治療方法,，這種方法將可能顯著的促進現(xiàn)有的技術,。
該療法基于一一組分子能調控免疫反應遏制監(jiān)管手臂卻增強保護手臂，允許誘導一種特定的白細胞（被稱為殺手T細胞）靶向并清除腫瘤,。這種新的疫苗方法在臨床前階段治療一系列的癌癥小鼠模型實驗中非常有效,。
研究結果發(fā)表于本月在線《癌癥研究》上，這些發(fā)現(xiàn)已被專利保護,，同時Mills教授已計劃將它們轉化到臨床應用,。( 生物谷bioon.com)
doi:10.1158/0008-5472
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Immunotherapy with PI3K inhibitor and Toll-like receptor agonist induces IFN-γ+IL-17+ polyfunctional T-cells that mediate rejection of murine tumors
Neil A Marshall, Karen C Galvin, Anna-Maria B Corcoran, Louis Boon, Rowan Higgs, and Kingston H.G. Mills
Abstract： The immunosuppressive microenvironment in tumors hampers the induction of anti-tumor immunity by vaccines or immunotherapies. TLR ligands have the potential to treat tumors, but they can exert a mixture of positive and negative effects on inflammation in the tumor microenvironment. In this study we show that specific small molecule inhibitors of PI3K relieve immunosuppression to heighten the pro-inflammatory effects of TLR ligands that support anti-tumor immunity. Multiple strategies to inhibit PI3K in dendritic cells (DC) each led to suppression of IL-10 and TGF-β but did affect IL-12 or IL-1β induction by the TLR5 ligand flagellin. In three different mouse models of cancer, combining flagellin with a class-I PI3K inhibitor, either with or without a DC vaccine, delayed tumor growth and increased survival, with some animals exhibiting complete rejection and resistance to secondary challenge. Tumor growth suppression was associated with increased accumulation of polyfunctional T cells that secreted multiple effector cytokines, including IFN-γ, IL-17 and IL-2. Therapeutic protection was abolished in mice deficient in IL-17 or deprived of IFN-γ. Together, our results indicate that PI3K inhibition heighten the anti-tumor properties of TLR ligands, eliciting tumor regression directly but also indirectly by relieving suppressive signals that restrict potent anti-tumor T cell responses. These findings suggest important uses for PI3K inhibitors in heightening responses to cancer immunotherapy and immunochemotherapy. Received January 26, 2011. Revision received November 17, 2011. Accepted November 29, 2011.
