Long-Acting IFN-gamma for Treating Immunodeficiencies

描述(申请人提供)：干扰素-γ是一种T细胞衍生的细胞因子，在许多细胞类型上表现出抗病毒和免疫调节作用。重组人干扰素-γ被批准用于治疗慢性肉芽肿性疾病和严重的恶性骨化症。目前正在研究的其他非人类临床试验的适应症包括特发性肺纤维化、肝纤维化、丙型肝炎和卵巢癌。 干扰素-γ在皮下给药后半衰期短(25-35分钟)，需要频繁给药并降低潜在疗效。我们建议创造聚合物修饰的干扰素-伽马蛋白，与现有的干扰素-伽马产品相比，可以更少地使用，但具有更大的效力。在第一阶段，我们将确定干扰素-γ中可以在不影响蛋白质体外生物活性的情况下进行修饰的位置。在第二阶段，我们将开发制造工艺，生产足够数量的修改后的干扰素-伽马蛋白，用于动物疾病模型的测试。新型干扰素-伽马蛋白的改进特性应该会减少每个患者所需的干扰素伽马量，提高疗效，降低毒性，改善患者的依从性和生活质量，并为患者和医疗保健提供者节省大量成本。干扰素-γ是结构相关的生长因子和细胞因子大家族中的一员。从这些研究中获得的信息将有助于创建该基因家族其他成员的长效版本，用于治疗癌症、传染病和血液系统疾病

DESCRIPTION (provided by applicant): Interferon-gamma is a T cell-derived cytokine that exhibits anti-viral and immunomodulatory effects on many cell types. Recombinant human interferon-gamma is approved for the treatment of chronic granulomatous disease and severe malignant osteopetrosis. Other indications currently being investigated inhuman clinical trials include idiopathic pulmonary fibrosis, liver fibrosis, hepatitis C and ovarian cancer. Interferon-gamma has a short half-life after subcutaneous administration (25-35 min) that necessitates frequent administration and reduces potential efficacy. We propose to create polymer modified interferon-gamma-proteins that can be administered less frequently, but with greater potency, than existing interferon-gamma products. During Phase I we will identify sites in interferon-gamma that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will develop manufacturing processes to produce sufficient quantities of the modified interferon-gamma proteins for testing in animal disease models. The improved characteristics of the novel interferon-gamma proteins should reduce the amount of interferon gamma required per patient, enhance efficacy, reduce toxicity, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. Interferon-gamma is a member of a large family of structurally related growth factors and cytokines. Information gained from these studies will aid in creating long-acting versions of other members of this gene family for use in treating cancer, infectious disease and hematopoietic disorders