据12月21日医疗快线报道，爱尔兰都柏林三一学院的科学家开发出一种新的疫苗用于在临床前阶段治疗癌症。研究组由都柏林三一学院实验免疫学教授Kingston Mills领导，他们发现了一种新的方法来治疗疾病，这种新方法基于调控机体对恶性肿瘤的免疫反应。这一发现已申请专利，并且计划开发出疫苗供癌症患者临床使用。
第一种疫苗Sipuleucel-T（Provenge）于去年通过许可用于对激素治疗无效的前列腺癌患者。不幸的是，这种基于细胞的疫苗仅提高了患者平均4.1个月的生存率。疫苗对感染性疾病产生了非常有效免疫反应，阻止了细菌或病毒的感染。免疫系统同样也能保护机体对抗肿瘤，理论上疫苗方法应该对癌症有效。在实际中，这已被证明是非常难的，因为肿瘤不像感染性疾病，它是起源于正常的人体细胞，并不是由外源物质或能够触发免疫反应的抗原组成。相反肿瘤细胞产生了能抑制免疫系统功效的分子。他们产生调节性细胞抑制了能潜在清除肿瘤的免疫反应。
Mills教授研究小组已经开发了一种能克服这些障碍的新型疫苗以及免疫治疗方法，这种方法将可能显著的促进现有的技术。
该疗法基于一一组分子能调控免疫反应遏制监管手臂却增强保护手臂，允许诱导一种特定的白细胞（被称为杀手T细胞）靶向并清除肿瘤。这种新的疫苗方法在临床前阶段治疗一系列的癌症小鼠模型实验中非常有效。
研究结果发表于本月在线《癌症研究》上，这些发现已被专利保护，同时Mills教授已计划将它们转化到临床应用。( 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.
