DEVELOPMENTOF CHEMOKINES FOR MYELOPROTECTION

用于骨髓保护的趋化因子的开发

• 批准号: 2109799
• 负责人: THOMAS J DALY
• 金额: $ 10万
• 依托单位: REPLIGEN CORPORATION
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-03-24 至 1995-09-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2109799
• 关键词: antineoplastics; biomaterial development /preparation; cell growth regulation; chemoprevention; chimeric proteins; hematopoietic stem cells; laboratory mouse; mutant; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; peptide analog; protein structure function

DESCRIPTION: The long term goal of the project is to develop a myelostatic agent to protect human hematopoietic precursor cells from the destructive effects of chemotherapeutic agents currently used in the treatment of tumors. The Applicants propose that protection of precursor cells by inhibition of growth during cancer treatment would reduce the toxicity associated with standard chemotherapy or permit the administration of higher doses of chemotherapeutics without compromising the ability of the patient to regenerate mature functional blood cells. They have identified a family of novel chemokine-based agents, which reversibly inhibit human stem cell proliferation in vitro at very low concentrations. Their initial plan is to test the agents' efficacy for temporarily inhibiting proliferation of murine hematopoietic progenitor cells in vivo. Successful completion of this goal may lead directly to a new clinical candidate. In parallel, the Applicants propose to express, purify, and test in an in vitro stem cell proliferation assay additional novel agents. The hypothesis is that the determination of the protein domains within the chemokine proteins which are required for biological activity will lead to peptide mimetics or small organic molecule drug candidates for evaluation in both in vitro and in vivo assays to assess their clinical potential.

描述：该项目的长期目标是开发一种 抗髓药用于保护人造血祖细胞免受 目前使用的化疗药物的破坏性作用 肿瘤的治疗。申请人建议对前体的保护 在癌症治疗过程中通过抑制生长来减少细胞 与标准化疗相关的毒性或允许 在不妥协的情况下给予更高剂量的化疗药物 患者再生成熟功能血细胞的能力。 他们已经确定了一系列基于趋化因子的新型药物，这些药物 极低浓度可逆性抑制人干细胞体外增殖 浓度。他们最初的计划是测试这些试剂对 暂时抑制小鼠造血祖细胞的增殖 体内的细胞。成功完成这一目标可能会直接导致 一位新的临床候选人。同时，申请人建议表达， 纯化，并在体外干细胞增殖试验中进行测试 新奇的特工。假设是蛋白质的测定 趋化因子蛋白中生物学所需的结构域 活性会导致多肽模拟物或有机小分子药物 在体外和体内试验中进行评估的候选对象 他们的临床潜力。