Resource for Nonhuman Primate Cell Depleting Antibodies

非人灵长类细胞耗竭抗体资源

• 批准号: 8118640
• 负责人: KEITH A. REIMANN
• 金额: $ 34.8万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-12 至 2011-08-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8118640
• 关键词: Animal Model; Antibodies; Biomedical Research; Callithrix; Cells; Cercopithecus pygerythrus; Contracts; Discipline; Disease; Drug Kinetics; Funding; Genes; Grant; Immunoglobulin G; Institutes; Intramural Research Program; Knock-out; Lymphocyte Subset; Macaca mulatta; Methods; Modeling; Monoclonal Antibodies; National Institute of Allergy and Infectious Disease; Papio; Pathogenesis; Primates; Production; Protein Engineering; Reagent; Recombinant Antibody; Recombinants; Research; Research Personnel; Research Project Grants; Resources; Technology; Testing; Transgenic Organisms; United States National Institutes of Health; Vaccine Therapy; antibody engineering; base; expression vector; immune function; immunogenicity; improved; in vivo; multidisciplinary; next generation; nonhuman primate; programs; public health relevance

DESCRIPTION (provided by applicant): Nonhuman primates (NHPs) continue to serve as 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 small animal models. Over the past decade, the number of NIH-funded research projects employing NHPs has increased by 50%. However, in the absence of readily available transgenic or gene knock-out primates, the utility of the NHP models is often limited by the availability of reagents capable of in vivo modulation of specific immune functions. In the preceding funding periods, this grant established the NIH Nonhuman Primate Reagent Resource, a program for developing and distributing antibody-based reagents that deplete specific lymphocyte subpopulations or target specific immune functions in vivo. In the past three years, this program has developed methods for generating and producing rhesus recombinant monoclonal antibodies with reduced immunogenicity and improved pharmacokinetics. Over this period, we distributed nearly 200 grams of antibody reagents supporting 48 NIH grants or intramural programs representing 8 NIH institutes or centers, and 11 non-NIH-funded programs. Furthermore, the technologies developed through this grant are also being utilized by an NIAID reagent contract which further supports investigators who use NHP models. As the need for these unique reagents continues to grow, new methods in protein engineering and expression are also emerging that will allow us to develop engineered antibodies with more focused targeting of cell subpopulations, defined effector function, and to produce them using more efficient expression methods. To continue support of NHP models across multidisciplinary scientific programs we will: 1. Develop "next generation", engineered antibodies for targeting and depleting the major lymphocyte subsets in NHP 2. Engineer antibody Fc regions to modulate effector function 3. Generate fully rhesus monoclonal antibodies and explore the diversity of rhesus IgG 4. Produce IgG expression vectors for baboon, African green monkey and marmoset to enable production of recombinant antibodies for use in these other NHP species 5. Continue to produce and distribute these reagents to investigators using NHP models PUBLIC HEALTH RELEVANCE (provided by applicant): This program will facilitate better utilization of nonhuman primate models by developing and distributing unique research reagents, and support biomedical research across a wide range of scientific disciplines.

描述（由申请人提供）：非人灵长类动物（NHP）继续作为探索感染性和非感染性疾病发病机制以及测试无法在小动物模型中评价的新疗法和疫苗的强大动物模型。在过去的十年中，NIH资助的研究项目数量增加了50%。然而，在缺乏容易获得的转基因或基因敲除灵长类动物的情况下，NHP模型的实用性通常受到能够在体内调节特异性免疫功能的试剂的可用性的限制。在之前的资助期间，这笔赠款建立了NIH非人灵长类动物试剂资源，这是一个用于开发和分发基于抗体的试剂的计划，这些试剂可以消耗特定的淋巴细胞亚群或靶向体内特定的免疫功能。在过去的三年中，该计划已经开发了用于产生和生产具有降低的免疫原性和改善的药代动力学的恒河猴重组单克隆抗体的方法。在此期间，我们分发了近200克抗体试剂，支持代表8个NIH研究所或中心的48个NIH赠款或校内项目，以及11个非NIH资助的项目。此外，通过该赠款开发的技术也被NIAID试剂合同所利用，该合同进一步支持使用NHP模型的研究人员。随着对这些独特试剂的需求持续增长，蛋白质工程和表达的新方法也在出现，这将使我们能够开发具有更集中的细胞亚群靶向、定义的效应子功能的工程抗体，并使用更有效的表达方法来生产它们。为了继续支持跨多学科科学计划的NHP模型，我们将：1。开发“下一代”工程抗体，用于靶向和消耗NHP 2中的主要淋巴细胞亚群。工程化抗体Fc区以调节效应子功能3.制备恒河猴单克隆抗体，探讨恒河猴IgG的多样性4.为狒狒、非洲绿色猴和绒猴生产IgG表达载体，以生产用于其他NHP物种的重组抗体5。继续使用NHP模型生产并向研究者分发这些试剂 公共卫生相关性（由申请人提供）：该计划将通过开发和分发独特的研究试剂，促进更好地利用非人灵长类动物模型，并支持广泛的科学学科的生物医学研究。