LONG-ACTING GM-CSF PROTEINS FOR TREATING NEUTROPENIA

描述：（研究者摘要）粒细胞-巨噬细胞集落 刺激因子（GM-CSF）是一种刺激细胞增殖和增殖的细胞因子。 造血祖细胞的分化。重组人GM-CSF， 用于刺激中性粒细胞减少症患者的中性粒细胞生成， 因为骨髓抑制化疗重组人GMCSF在世界范围内 1997年的销售额约为1亿美元， 1996.我们建议创建修改后的GM-CSF蛋白质， 天然GM-CSF刺激体内粒细胞/单核细胞形成，但 其需要较低频率的给药，大约每周一次或每隔一周一次， 其他的星期。在第一阶段，我们确定了GM-CSF中可以修饰的位点， 而不影响蛋白质的体外生物活性。在第二阶段，我们将 制备足够量的用于测试的修饰的GM-CSF蛋白 中性粒细胞减少症的动物模型。小说的改良特征 GM-CSF蛋白将减少每个患者所需的GM-CSF的量， 患者依从性和生活质量，并节省大量成本 to patients患者and healthcare健康providers提供者.从这些研究中获得的信息 将有助于产生结构相关细胞因子的长效版本， 用于治疗癌症、感染性疾病和造血干细胞疾病的生长因子 紊乱 拟定商业应用： 重组人GM-CSF用于恢复患有以下疾病的患者的中性粒细胞产生： 化疗或骨髓移植导致的中性粒细胞减少症。 重组 1997年，GM-CSF的全球销售额超过1亿美元。 改良的GM-CSF 开发中的蛋白质将需要更少的剂量， 为患者和医疗保健提供者节省成本。 其他潜在好处包括 提高了药物功效并提高了患者的生活质量。

DESCRIPTION: (Investigator's abstract) Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a cytokine that stimulates proliferation and differentiation of hematopoietic progenitor cells. Recombinant human GM-CSF is used to stimulate neutrophil production in patients with neutropenia resulting from myelosuppressive chemotherapy. Recombinant human GMCSF had world-wide sales of approximately $100 million during 1997, a 20 percent increase from 1996. We propose to create modified GM-CSF proteins that are equal or superior to natural GM-CSF at stimulating granulocyte/monocyte formation In vivo, but which require less frequent dosing, on the order of once per week or once every other week. During Phase I we identified sites in GM-CSF that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will manufacture sufficient quantities of the modified GM-CSF proteins for testing in animal models of neutropenia. The improved characteristics of the novel GM-CSF proteins will reduce the amount of GM-CSF required per patient, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. Information gained from these studies will aid in creating long-acting versions of structurally related cytokines and growth factors for use in treating cancer, infectious disease and hematopoietic disorders. PROPOSED COMMERCIAL APPLICATION: Recombinant human GM-CSF is used to restore neutrophil production in patients with neutropenia resulting from chemotherapy or bone marrow transplantation. Recombinant GM-CSF had world-wide sales in excess of $100 million in 1997. The modified GM-CSF proteins under development will require much less frequent dosing, providing significant cost savings to patients and healthcare providers. Additional potential benefits include improved drug efficacy and improved patient quality of life.