Development of Amygdala specific monoclonal Antibodies

杏仁核特异性单克隆抗体的开发

• 批准号: 6549671
• 负责人: Andreas H Kottmann
• 金额: $ 12.39万
• 依托单位: PSYCHOGENICS, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-12 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6549671
• 关键词: amygdala; biotechnology; immune tolerance /unresponsiveness; immunization; immunologic substance development /preparation; immunomodulators; laboratory rat; nerve /myelin protein; western blottings

DESCRIPTION (provided by applicant): In this application we propose to use "Differential Immunization for Antigen and Antibody Discovery" (DIAAD) technology, a novel differential immunization method established by Vacold L.L.C., and generate rat monoclonal antibodies to epitopes specific to the Amygdala of mice. DIAAD is enabled by the Virtual Lymph Node (VLN), an implantable device used as a powerful immunological adjuvant with sensitivity to minute doses of antigen. The dose of antigen with which the VLN are loaded prior to implantation determines whether the immune reaction leads to a positive immune response, anergys or tolerance. The DIAAD technology is sensitive to antigens of broad chemical diversity, i.e., lipids, carbohydrate, gangliosides, proteins, and posttranslational protein modifications. Hence this technology allows us to tolerize the immune system against immuno-dominant and ubiquitously expressed epitopes and to direct the immune system towards less immunogenic but tissue specifically expressed antigens starting with complex mixtures of antigens. We chose the Amygdala as a target tissue since it is a central component of the structures, which consolidate and express emotions and has been implicated in the pathogenesis of affective mental disorders including depression. The possible importance of the Amygdala in the manifestation of affective mental disorders has been recognized for some time. Hence, there is a large scientific community both in the public and private sector, which devotes its resources to Amygdala research. One of the key objectives of the neuro-pharmaceutical industry is to develop novel therapeutics for the treatment of affective mental disorders. The specific aim of the proposed experiments is: to develop novel research tools for both applied and basic biomedical research in form of rat Monoclonal Antibodies (Moab's) against Amygdala specific epitopes of mice. The defined Milestone at the end of this phase 1 application is: to demonstrate the capacity to derive Amygdala specific MoAbs by differential tolerization /immunization using DIAAD and VLN technologies. These MoAbs should be usable for cytohistochemistry and/or western blot applications. We believe that these MoAbs will greatly accelerate research aimed to elucidate mechanisms of function of the Amygdala and will find widespread use in academic and industrial research. In a phase II extension of this application we wish to expand our portfolio of MoAbs reagents based on our results from phase I covering other important brain regions for human psychiatric diseases. In addition, we want to develop reagents to plastic changes of brain tissues in the context of inducible animal models with relevance to human psychiatric diseases.

描述（由申请人提供）：在本申请中，我们建议使用“抗原和抗体发现的差异免疫”（DIAAD）技术，这是Vacold L.L.C.建立的一种新颖的差异免疫方法，并产生针对杏仁核特异性表位的大鼠单克隆抗体老鼠。 DIAAD 由虚拟淋巴结 (VLN) 实现，这是一种可植入的设备，用作强大的免疫佐剂，对微量抗原敏感。植入前 VLN 加载的抗原剂量决定了免疫反应是否导致阳性免疫反应、无反应性或耐受性。 DIAAD 技术对广泛化学多样性的抗原敏感，即脂质、碳水化合物、神经节苷脂、蛋白质和翻译后蛋白质修饰。因此，这项技术使我们能够耐受免疫显性和普遍表达的表位的免疫系统，并从复杂的抗原混合物开始引导免疫系统针对免疫原性较低但组织特异性表达的抗原。 我们选择杏仁核作为目标组织，因为它是巩固和表达情绪的结构的核心组成部分，并且与包括抑郁症在内的情感性精神障碍的发病机制有关。一段时间以来，人们已经认识到杏仁核在情感性精神障碍的表现中可能的重要性。因此，公共和私营部门都有一个庞大的科学界，将其资源投入到杏仁核研究中。神经制药行业的主要目标之一是开发治疗情感性精神障碍的新疗法。 拟议实验的具体目的是：以针对小鼠杏仁核特定表位的大鼠单克隆抗体（Moab's）的形式开发用于应用和基础生物医学研究的新型研究工具。 第一阶段应用结束时定义的里程碑是：证明使用 DIAAD 和 VLN 技术通过差异耐受/免疫获得杏仁核特异性 MoAb 的能力。这些 MoAb 应可用于细胞组织化学和/或蛋白质印迹应用。 我们相信，这些单克隆抗体将大大加速旨在阐明杏仁核功能机制的研究，并将在学术和工业研究中得到广泛应用。在该应用的第二阶段扩展中，我们希望根据第一阶段的结果扩展我们的 MoAbs 试剂组合，涵盖人类精神疾病的其他重要大脑区域。此外，我们希望在与人类精神疾病相关的诱导动物模型中开发脑组织塑性变化的试剂。