SPECIFIC DEPLETION OF STEM CELLS FACILITATES ENGRAFTMENT

干细胞的特异性消耗有利于移植

• 批准号: 6486314
• 负责人: JULIAN DAVID DOWN
• 金额: $ 10万
• 依托单位: BIOTRANSPLANT, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6486314
• 关键词: blood cell depletion therapy; flow cytometry; graft versus host disease; hematopoietic stem cells; human tissue; laboratory mouse; monoclonal antibody; stem cell transplantation

DESCRIPTION (provided by applicant): Allogeneic stem cell transplantation has broad implications as a therapeutic strategy for treating diseases such as cancer, autoimmune disease, and genetic disorders as well as for induction of specific immune tolerance for transplanted solid organs. A number of previous experimental studies have shown that depletion of primitive stem cells is often required in the host before long-term engraftment (chimerism) from donor stem cells is achieved. In myeloablative protocols, this is accomplished with high doses of irradiation or pharmacological agents such as busulfan. Many non-myeloablative protocols currently being evaluated depend, at least in part, on mature T cells present in the donor graft to provide this function. Engraftment achieved in this manner, however, is often associated with graft-versus-host disease (GVHD). Our goal in this Phase I proposal is to demonstrate proof of concept that a monoclonal antibody specifically directed against hematopoietic stem cells of the recipient can be substituted for toxic agents such as busulfan, thus eliminating the requirement for donor T cells in non-myeloablative transplant protocols and reducing the likelihood of GVHD. Phase II will be proof of concept in a relevant primate model of allogeneic stem cell transplantation.

描述(申请人提供)：异基因干细胞移植 作为治疗疾病的一种治疗策略，如 癌症、自身免疫性疾病和遗传性疾病以及 移植实体器官的特异性免疫耐受。一些以前的 实验研究表明，原始干细胞的枯竭通常是 供体干细胞长期植入(嵌合体)前宿主所需 细胞是实现的。在清髓方案中，这是通过高水平的 辐射剂量或药理药剂，如丁硫丹。许多 目前正在评估的非清髓性方案至少部分地取决于， 在供者移植物中存在的成熟T细胞上提供这种功能。 然而，以这种方式实现的嫁接通常与 移植物抗宿主病(GVHD)。我们在此第一阶段提案中的目标是 证明概念上的证据，即一种单抗专门针对 针对受者的造血干细胞可替代毒性 白花丹等制剂，从而消除了对供体T细胞的需求 非清髓性移植方案和降低移植物抗宿主病的可能性。 第二阶段将在相关的异基因灵长类动物模型中进行概念验证 干细胞移植。