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: 10540237
• 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/10540237
• 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; Online Systems; Organ Transplantation; Pathogenesis; Pharmaceutical Preparations; Play; Preclinical Testing; Program Effectiveness; Quality Control; R24; 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; large scale production; manufacture; 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.

项目概要-总体 非人灵长类动物（NHP）在历史上一直是疾病和测试的重要动物模型 新的治疗方法和疫苗，不能在小动物模型中进行评估。NHP模型在 通过使用免疫细胞耗竭抗体， 在体内裂解特定的细胞亚群。在传染病模型和疫苗测试中，靶向免疫细胞 耗尽已被用来了解这些感染的发病机制，并设计更好的疫苗， 防止他们。此外，细胞去除可以是有效的免疫调节疗法和临床前治疗。 这些细胞消耗抗体药物的测试通常在非人灵长类动物中进行。 在过去的18年里，NIH一直支持非人灵长类动物试剂资源的努力， 通过R24表征、生产和分发用于NHP模型的免疫细胞消耗抗体 格兰特.自成立以来，该计划活动的逐年增长证实了对该计划的需求。 在过去的一年里，这笔赠款满足了超过125项细胞耗竭抗体试剂的申请，至少支持了 50种不同的NIH赠款或项目。向NHP施用近400克细胞消耗抗体， 发放 这项拨款建议继续这项计划，提供用于NHP的免疫细胞耗竭抗体， 维持免疫细胞消耗抗体和对照抗体的大规模生产和质量控制。 我们还将开发针对新靶点的抗体，并通过工程改造改进现有抗体， 有效的消耗。我们基于网络的基础设施将用于广告试剂，接收和履行 要求，并衡量计划的有效性。努力提高严谨性和透明度， 将通过促进关键生物资源的认证来实现可重复性。最后我们将 开展应用研究，通过探索提高细胞耗竭抗体效应功能的方法， 细胞毒