Nonhuman Primate Antibody Resource for Immune Cell Depletion

项目摘要--总体 非人灵长类动物历来是疾病和测试的重要动物模型。 无法在小动物模型中进行评估的新疗法和疫苗。NHP模型在我国的应用 免疫细胞耗竭抗体的使用大大加强了研究，这种抗体可以靶向和 体内特异性细胞亚群的裂解。在传染病模型和疫苗测试中，靶向免疫细胞 耗竭已经被用来理解这些感染的发病机制，并设计出更好的疫苗来 阻止他们。此外，细胞耗竭是一种有效的免疫调节疗法，临床前 对这些耗尽细胞的抗体药物的测试通常在非人类灵长类动物身上进行。 在过去的18年里，NIH一直支持非人灵长类试剂资源的努力， 通过R24鉴定、制造和分发用于NHP模型的免疫细胞耗尽抗体 格兰特。自计划开始以来，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项细胞耗尽抗体试剂的申请，至少支持了 50种不同的NIH拨款或计划。用于注射NHP的近400克细胞耗尽抗体是 分布式的。 这笔赠款建议继续这一计划，通过以下方式提供免疫细胞耗尽抗体用于卫生保健计划 保持免疫细胞耗竭抗体和对照抗体的规模化生产和质量控制。 我们还将开发针对新靶点的抗体，并通过设计更多的抗体来改进现有抗体 高效耗尽。我们基于网络的基础设施将用于广告代理、接收和履行 请求，并衡量计划的有效性。努力加强严谨性和透明度，以改进 将通过促进关键生物资源的认证来实现可重复性。最后，我们会 通过探索改进方法来增强细胞耗竭抗体的效应器功能 细胞毒性。

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.