Nonhuman Primate Antibody Resource for Immune Cell Depletion

用于消除免疫细胞的非人灵长类动物抗体资源

• 批准号: 10320747
• 负责人: Kathleen Engelman
• 金额: $ 62.1万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320747
• 关键词: Advertising; Animal Disease Models; Animal Model; Antibodies; Applied Research; Basic Science; Biological; Cell physiology; Cells; Communicable Diseases; Disease; Genetic Polymorphism; Grant; Growth; Half-Life; Immune; Immune Targeting; Infection; Infrastructure; Measures; Methods; Modeling; Monoclonal Antibody R24; Online Systems; Organ Transplantation; Pathogenesis; Pharmaceutical Preparations; Play; Preclinical Testing; Program Effectiveness; Quality Control; Reagent; Reproducibility; Research; Research Personnel; Resources; Rhesus; Role; Testing; Therapeutic antibodies; Translational Research; United States National Institutes of Health; Vaccines; antibody engineering; cytotoxicity; design; immunomodulatory therapies; improved; in vivo; infectious disease model; nonhuman primate; novel therapeutics; novel vaccines; prevent; programs; receptor; vaccine evaluation

Project Summary – Overall Nonhuman primates (NHPs) have historically served as crucial animal models for diseases, and for testing of new therapies and vaccines that cannot be evaluated in small animal models. The utility of NHP models in research has been enhanced considerably by the use of immune cell depleting antibodies that can target and lyse specific cell subsets in vivo. In models of infectious disease and vaccine testing, targeted immune cell depletion has been used understand the pathogenesis of these infections and to design better vaccines to prevent them. Furthermore, cell depletion can be an effective immune modulating therapy and the preclinical testing of these cell-depleting antibody drugs is often conducted in nonhuman primates. For the past 18 years, NIH has supported the Nonhuman Primate Reagent Resource’s efforts to develop, characterize, manufacture and distribute immune cell depleting antibodies for use NHP models through a R24 grant. Need for this program has been confirmed by year-over-year growth in program activity since its inception. Over the past year, this grant fulfilled over 125 requests for cell-depleting antibody reagents, supporting at least 50 different NIH grants or programs. Nearly 400 grams of cell-depleting antibody for administration to NHP was distributed. This grant proposes to continue this program providing immune cell depleting antibodies for use in NHPs by maintaining the large-scale manufacture and quality control of the immune cell-depleting and control antibodies. We will also develop antibodies against new targets and improve existing antibodies by engineering for more efficient depletion. Our web-based infrastructure will be used for advertising reagents, receiving and fulfilling requests, and measuring program effectiveness. Efforts to enhance rigor and transparency to improve reproducibility will be accomplished by facilitating the authentication of key biological resources. Finally, we will conduct applied research to enhance effector function of cell-depleting antibodies by exploring way to improve cytotoxicity.

项目摘要 - 总体 非人类灵长类动物（NHP）历史上一直是疾病的关键动物模型，并进行了测试 在小动物模型中无法评估的新疗法和疫苗。 NHP模型的实用性 通过使用可以靶向和靶向的免疫细胞耗尽抗体，仔细地增强了研究 在体内裂解特定的细胞子集。在传染病和疫苗测试的模型中，有针对性的免疫细胞 耗竭已被用来了解这些感染的发病机理，并将更好的疫苗设计为 防止他们。此外，细胞耗竭可能是一种有效的免疫调节疗法，临床前的疗法 这些缺乏细胞的抗体药物的测试通常是在非人类隐私中进行的。 在过去的18年中，NIH支持了非人类灵长类试剂资源的发展， 表征，制造和分发免疫核管通过R24使用NHP型号耗尽抗体 授予。自计划活动以来，该计划的需求已被计划活动的同比增长所证实。 在过去的一年中，这笔赠款满足了125种耗尽细胞抗体试剂的要求，至少支持 50种不同的NIH赠款或计划。用于NHP给药的近400克细胞耗尽抗体 分布式。 这项赠款提案继续该程序，提供免疫细胞耗尽抗体，以在NHP中使用 维持免疫细胞耗尽和控制抗体的大规模制造和质量控制。 我们还将开发针对新目标的抗体，并通过工程技术来改善现有抗体 有效的耗竭。我们的基于网络的基础架构将用于广告试剂，接收和实现 请求和衡量计划效率。提高严格和透明度的努力以改善 可重复性将通过支持关键生物资源的身份验证来实现。最后，我们会的 通过探索改进的方法来进行应用研究以增强细胞耗尽抗体的效应子功能 细胞毒性。