Resource for Nonhuman Primate Cell Depleting Antibodies

非人灵长类细胞耗竭抗体资源

• 批准号: 7900648
• 负责人: KEITH A. REIMANN
• 金额: $ 37.62万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-17 至 2010-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7900648
• 关键词: Resource; Nonhuman; Primate; Cell; Depleting

DESCRIPTION (provided by applicant): Nonhuman primates (NHPs) provide powerful animal models for exploring the pathogenesis of infectious and noninfectious diseases, and for testing of new therapies and vaccines that cannot be evaluated in rodents. Over the past decade, the number of NIH grants employing nonhuman primates has doubled. However, the utility of these models in many cases is limited by the availability of reagents for in vitro diagnostics and for in vivo modulation of specific immune functions. During the previous funding period of this grant, we established the NIH Nonhuman Primate Reagent Resource, a program for identifying and/or developing monoclonal antibodies, including new mouse-human chimeric recombinant monoclonal antibodies, fully-human monoclonal antibodies and rhesus receptor/human Ig fusion proteins that deplete specific lymphocyte subpopulations or target specific immune functions in vivo. We also established processes for large-scale production of reagents and optimized their use. During this initial award period, we distributed 90,000 milligrams of purified monoclonal antibody supporting more than 60 NIH grants or intramural programs representing 8 NIH institutes or centers. The need for these unique reagents has grown steadily since the initiation of this program. In addition, the potential has emerged to develop new reagents with reduced antigenicity, longer duration of effect in vivo and more focused targeting of lymphocyte subpopulations. To continue support of nonhuman primate models across multidisciplinary scientific programs we will: 1) Produce and distribute recombinant antibodies and fusion proteins developed during the previous funding period, 2) Identify and/or develop reagents, including recombinant (chimeric, humanized and primatized) mAbs, with new specificities and functions as directed by a scientific advisory committee, 3) Develop macaque IgG vectors for generating recombinant rhesus antibodies and rhesus Ig-Fc fusion proteins, and assess the in vivo biological properties of recombinant rhesus lgG1, lgG2 and lgG4 antibodies, 4) Explore methods of increasing recombinant antibody plasma half-life by increasing affinity for FcRn, and 5) Determine if experimental lymphocyte depletion reactivates viruses that are endemic in captive NHPs potentially affecting experimental outcome or having public health considerations.

描述（由申请人提供）：非人类灵长类动物（NHP）提供了强大的动物模型，用于探索传染病和非感染性疾病的发病机理，并测试无法在啮齿动物中评估的新疗法和疫苗。在过去的十年中，采用非人类灵长类动物的NIH赠款数量增加了一倍。但是，在许多情况下，这些模型的实用性受到体外诊断和体内特定免疫功能调节的试剂的可用性的限制。 During the previous funding period of this grant, we established the NIH Nonhuman Primate Reagent Resource, a program for identifying and/or developing monoclonal antibodies, including new mouse-human chimeric recombinant monoclonal antibodies, fully-human monoclonal antibodies and rhesus receptor/human Ig fusion proteins that deplete specific lymphocyte subpopulations or target specific immune functions体内。我们还建立了大规模生产试剂并优化其使用的过程。在这个初始奖励期间，我们分发了90,000毫克纯化的单克隆抗体，支持60多个NIH赠款或代表8个NIH机构或中心的壁内计划。 自从该程序启动以来，对这些独特的试剂的需求稳步增长。此外，已经出现了潜力，以开发抗原性降低，体内效果较长的新试剂以及对淋巴细胞亚群的靶向更为集中的。为了继续支持多学科科学计划的非人类灵长类动物模型，我们将：1）生产和分发在上一个融资期间开发的重组抗体和融合蛋白，2）确定和/或开发试剂，包括重组（嵌合，人性化和原始人），包括新的特定委员会，包括新的特定委员会，以实现科学的委员会，3），3）重组的恒和氏抗体和颗粒状Ig-Fc融合蛋白，并评估重组LGG1，LGG2和LGG4抗体的体内生物学特性，4）探索方法的方法增加了重新组合抗体等离子体对FCRN的相关性，并确定IFCRN的相关性，并确定IFCRN的相关性。在圈养的NHP中，可能会影响实验结果或具有公共卫生考虑因素。