Enhanced Engraftment of Stem Cells

增强干细胞的植入

• 批准号: 7273369
• 负责人: Manley TF Huang
• 金额: $ 20.17万
• 依托单位: PANORAMA RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-08 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7273369
• 关键词: Address; Adhesions; Allogenic; Antibodies; Antigen Targeting; Antigens; Autologous; Bispecific Antibodies; Bone Marrow; Bone Marrow Cells; CD3 Antigens; CD34 gene; Cardiac; Cell Adhesion; Cell Adhesion Molecules; Cells; Clinical; Clinical Research; Clinical Trials; Data; Development; Disease; Engraftment; Facility Construction Funding Category; Failure; Genetic; Goals; Hematologic Neoplasms; Hematopoietic; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Homing; Human; Immunologic Deficiency Syndromes; Injection of therapeutic agent; Injury; Ischemia; Legal patent; Mediating; Medical center; Methods; Monoclonal Antibody HuM291; Morbidity - disease rate; Muromonab-CD3; Mus; Myocardium; Myosin Light Chains; Numbers; Outcome; Phase; Phase II Clinical Trials; Physiological reperfusion; Population; Preparation; Process; Production; Proto-Oncogene Protein c-kit; Recovery; Reperfusion Therapy; Rodent Model; Site; Stem cells; Surface; T-Lymphocyte; Technology; Therapeutic; Tissues; Toxicology; Umbilical Cord Blood; Work; base; chemokine; concept; cytokine; human stem cells; improved; in vivo; injured; irradiation; mortality; novel; peripheral blood; reconstitution; stem cell therapy; success

DESCRIPTION (provided by applicant): Enhanced engraftment of stem cells. There is an urgent need for methods to improve the engraftment efficiency of autologous and allogeneic hematopoietic stem cells (HSC) after myeloablative therapy. Although mobilized peripheral blood and umbilical cord blood (CB) have expanded the availability of donor cells, a significant cause of morbidity and mortality is the failure to obtain complete and rapid hematopoietic reconstitution. This is most often due to the injection of low numbers of CD34+ cells; insufficient homing, retention and differentiation of donor cells; and/or lack of facilitator cell help (T cell help in engraftment and/or other cell populations). To address these problems, we have developed a proprietary approach to cell targeting using bispecific antibodies (BiMab). A pair of antibodies is chemically heteroconjugated to target cells to specific antigens found at sites of injury. Our preliminary data have shown that three different BiMabs enhance the retention of targeted cells in vivo. In Phase I we will prepare an expanded set of BiMabs to demonstrate their ability to improve hematopoietic cell recovery and engraftment of irradiated mice. The BiMab that shows the greatest capacity to enhance engraftment will be selected for further development of a clinical candidate in Phase II. Enhanced engraftment of stem cells Hematopoietic stem cell (HSC) transplantation is a common therapeutic option developed to treat hematologic malignancies and certain genetic and immunological disorders. Efficient delivery, retention and differentiation of HSC remain major limitations to the success of bone marrow engraftment. Bispecific antibodies (BiMab) recognizing a bone marrow-specific target and an antigen on hematopoietic stem cells provide a novel means to greatly improve the efficiency of autologous and allogeneic stem cell therapy for a broad spectrum of diseases.

描述（由申请人提供）：增强干细胞植入。迫切需要提高清髓性治疗后自体和同种异体造血干细胞（HSC）的植入效率的方法。尽管动员的外周血和脐带血（CB）扩大了供体细胞的可用性，但发病率和死亡率的重要原因是未能获得完全和快速的造血重建。这通常是由于注射了少量的CD 34+细胞;供体细胞的归巢、保留和分化不足;和/或缺乏促进细胞帮助（T细胞帮助植入和/或其他细胞群）。为了解决这些问题，我们开发了一种使用双特异性抗体（BiMab）进行细胞靶向的专有方法。一对抗体通过化学方法与靶细胞结合，靶细胞与损伤部位的特异性抗原结合。我们的初步数据表明，三种不同的BiMab增强了靶细胞在体内的保留。在第一阶段，我们将准备一组扩大的BiMab，以证明它们能够改善受辐射小鼠的造血细胞恢复和移植。将选择表现出最大能力增强植入的BiMab用于II期临床候选药物的进一步开发。造血干细胞（HSC）移植是一种常见的治疗选择，用于治疗恶性血液病和某些遗传和免疫疾病。HSC的有效递送、保留和分化仍然是骨髓移植成功的主要限制。识别骨髓特异性靶标和造血干细胞上的抗原的双特异性抗体（BiMab）提供了一种新的手段，以大大提高自体和同种异体干细胞治疗广谱疾病的效率。