Whole recombinant yeast-based immunotherapy induces potent T cell responses targeting HCVNS3 and Core proteins
Whole recombinant yeast-based immunotherapy induces potent T cell responses targeting HCVNS3 and Core proteins
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DOI：
10.1016/j.vaccine.2006.10.035
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发表时间：
2007-02-09
期刊：
影响因子：
5.5
通讯作者：
Duke, Richard C.
中科院分区：
文献类型：
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作者：
Haller, Aurelia A.;Lauer, Georg M.;Duke, Richard C.
丙型肝炎病毒(HCV)原发感染的控制与强大和广泛的T细胞免疫有关。相比之下，慢性感染的特点是T细胞反应较弱，这表明增强这些反应的方法可能是一种治疗进步。酿酒酵母是天然和获得性细胞免疫的有效诱导者，我们已经产生了重组酵母细胞(GI-5005)，可以产生丙型肝炎病毒NS3-Core融合蛋白。小鼠的临床前研究表明，GI-5005诱导了与Th1型细胞因子分泌相关的强大的抗原特异性增殖性和细胞毒性T细胞反应。在使用GI-5005长达13次的研究中，没有观察到可检测到的载体中和或诱导耐受。GI-5005在小鼠体内的预防性和治疗性给药导致表达丙型肝炎病毒NS3蛋白的肿瘤细胞被根除。GI-5005的免疫疗法正在一期临床试验中用于慢性丙型肝炎病毒感染者。(C)2006爱思唯尔有限公司。保留所有权利。
Control of primary infection with hepatitis C virus (HCV) is associated with robust and broad T cell immunity. In contrast, chronic infection is characterized by weak T cell responses suggesting that an approach that boosts these responses could be a therapeutic advance. Saccharomyces cerevisiae is an effective inducer of innate and adaptive cellular immunity and we have generated recombinant yeast cells (GI-5005) that produce an HCV NS3-Core fusion protein. Pre-clinical studies in mice showed that GI-5005 induced potent antigen-specific proliferative and cytotoxic T cell responses that were associated with Th1-type cytokine secretion. In studies in which GI-5005 was administered up to 13 times, no detectable vector neutralization or induction of tolerance was observed. Prophylactic as well as therapeutic administration of GI-5005 in mice led to eradication of tumor cells expressing HCV NS3 protein. Immunotherapy with GI-5005 is being evaluated in chronic HCV infected individuals in a Phase 1 clinical trial. (c) 2006 Elsevier Ltd. All rights reserved.