MONOCLONAL ANTIBODIES FOR ALZHEIMER'S IMMUNOTHERAPY

用于阿尔茨海默病免疫治疗的单克隆抗体

• 批准号: 6885172
• 负责人: ANDREW C HIATT
• 金额: $ 29.51万
• 依托单位: MAPP BIOPHARMACEUTICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885172
• 关键词: Alzheimer' s disease; SDS polyacrylamide gel electrophoresis; amyloid proteins; behavior test; clinical research; disease /disorder model; enzyme linked immunosorbent assay; epitope mapping; genetically modified animals; genetically modified plants; immunologic substance development /preparation; immunotherapy; ion exchange chromatography; laboratory mouse; learning; memory; molecular cloning; monoclonal antibody; nonhuman therapy evaluation; polymerase chain reaction; protein metabolism; surface plasmon resonance; transfection /expression vector

DESCRIPTION (PROVIDED BY APPLICANT): Transgenic mice administered anti-amyloid peptide antibodies, acutely or subchronically, show markedly improved learning and memory performance. Recent reports suggest that the toxicity of the amyloid peptide and other amyloidogenic proteins lies not in the insoluble fibrils that accumulate but rather in the soluble oligomeric intermediates. A panel of monclonal antibodies has been developed by Mapp Biopharmaceutical, which recognizes the internal domain of soluble amyloid beta peptide. These antibodies are candidates for use in passive immunotherapy. The potential advantages of a passive approach include: (1) the dose of drug given to any patient can be determined precisely, eliminating potential variability which will occur with active immunization; (2) therapy can be started or stopped at any time. Potential disadvantages include: (1) whether enough reagent can be generated to treat large numbers of individuals and (2) cost. The purpose of this study is to evaluate a set of candidate monoclonal antibodies that are intended to contribute to our overall understanding of the benefits of passive Alzheimer's immunization in humans and produce these antibodies in a system, which ultimately minimizes the capital burden of antibody drug production and hence reduces the overall costs. In Specific Aim 1, the panel will be characterized with respect to affinity, oligomer binding, and epitope specificity. The variable regions of a selection of monoclonals will then be cloned in Specific Aim 2 and the genes introduced the into plant expression vectors as both mouse IgG and mouse-human chimeric IgG. Finally, in Specific Aim 3, the expression vectors will be introduced into plants to generate quantities of monoclonal sufficient for in vitro comparison to the original hybridoma expressed monoclonal.

描述（由申请人提供）：急性或下型的转基因小鼠施用抗淀粉样蛋白肽抗体，显示出明显改善的学习和记忆力表现。最近的报道表明，淀粉样蛋白肽和其他淀粉样蛋白蛋白的毒性不在于累积的不溶性原纤维，而是在可溶性的寡聚中间体中。 MAPP Biopharmaceutical开发了一系列蒙克隆抗体，该抗体识别可溶性淀粉样β肽的内部结构域。这些抗体是用于被动免疫疗法的候选物。被动方法的潜在优势包括：（1）可以精确确定给任何患者的药物剂量，从而消除主动免疫时会发生的潜在可变性； （2）可以随时开始或停止治疗。潜在的缺点包括：（1）是否可以生成足够的试剂来治疗大量个人和（2）成本。这项研究的目的是评估一组候选单克隆抗体，这些抗体旨在有助于我们对被动阿尔茨海默氏症对人类免疫接种的好处的整体理解，并在系统中产生这些抗体，最终使抗体药物生产的资本负担和因此减少了整体成本。在特定的目标1中，该面板将在亲和力，低聚物结合和表位特异性方面进行表征。然后，将单克隆选择的可变区域克隆到特定的目标2中，并且基因作为小鼠IgG和小鼠人类嵌合IgG引入植物表达载体。最后，在特定的目标3中，表达载体将被引入植物中，以产生足以与原始杂交瘤单克隆瘤进行体外比较的单克隆量。