Haller Aurelia A, Lauer Georg M, King Thomas H, Kemmler Charles, Fiolkoski Valerie, Lu Yingnian, Bellgrau Don, Rodell Timothy C, Apelian David, Franzusoff Alex, Duke Richard C
GlobeImmune, Inc., 1450 Infinite Drive, Louisville, CO 80027, USA.
Vaccine. 2007 Feb 9;25(8):1452-63. doi: 10.1016/j.vaccine.2006.10.035. Epub 2006 Nov 10.
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.
丙型肝炎病毒（HCV）原发性感染的控制与强大而广泛的T细胞免疫相关。相比之下，慢性感染的特征是T细胞反应较弱，这表明增强这些反应的方法可能是一项治疗进展。酿酒酵母是先天性和适应性细胞免疫的有效诱导剂，我们已经构建了产生HCV NS3-Core融合蛋白的重组酵母细胞（GI-5005）。在小鼠中进行的临床前研究表明，GI-5005可诱导强效的抗原特异性增殖和细胞毒性T细胞反应，这与Th1型细胞因子分泌有关。在给予GI-5005多达13次的研究中，未观察到可检测到的载体中和或耐受性诱导。在小鼠中预防性和治疗性给予GI-5005可导致表达HCV NS3蛋白的肿瘤细胞被清除。GI-5005免疫疗法正在一项1期临床试验中对慢性HCV感染个体进行评估。
