LONG-ACTING GM-CSF PROTEINS FOR TREATING NEUTROPENIA

描述：(研究人员摘要)粒细胞-巨噬细胞集落 刺激因子(GM-CSF)是一种细胞因子，可刺激细胞增殖和 造血祖细胞的分化。重组人GM-CSF是 用于刺激中性粒细胞减少症患者的中性粒细胞产生 来自骨髓抑制化疗。重组人GMCSF在世界范围内 1997年销售额约为1亿美元，较上年同期增长20% 1996年。我们建议创造同等或更好的修饰GM-CSF蛋白 对天然GM-CSF刺激体内粒/单核细胞形成，但 这些药物需要较少的频率给药，大约每周一次或每周一次 前几周。在第一阶段，我们确定了GM-CSF中可以修改的部位 而不影响蛋白质的体外生物活性。在第二阶段，我们将 生产足够量的GM-CSF修饰蛋白用于检测 在中性粒细胞减少症的动物模型中。这部小说改进后的特点 GM-CSF蛋白将减少每个患者所需的GM-CSF量，改善 患者依从性和生活质量，并节省大量成本 给病人和医疗保健提供者。从这些研究中获得的信息 将有助于创造与结构相关的细胞因子的长效版本 用于治疗癌症、传染病和造血的生长因子 精神错乱。 建议的商业应用： 重组人GM-CSF用于恢复慢性粒细胞白血病患者中性粒细胞的产生 化疗或骨髓移植引起的中性粒细胞减少症。重组 1997年，GM-CSF在全球的销售额超过1亿美元。改良型GM-CSF 正在开发中的蛋白质将需要更少的频率剂量，提供显著的 为患者和医疗保健提供者节省成本。其他潜在好处包括 改善药物疗效和改善患者的生活质量。

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.