RESOURCE FOR NONHUMAN PRIMATE CELL-DEPLETING ANTIBODIES

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。结合细胞表面分子的单克隆抗体的体内给药可以阻断由这些分子介导的作用，通过结合的分子递送刺激信号，或导致靶细胞群的耗竭。这种方法对于研究啮齿动物模型中的免疫致病事件非常有用。为了提高现有的非人灵长类动物疾病模型的有用性，我们已经开发了新的全人源单克隆抗体用于猕猴体内给药。这些新的抗体是通过克隆和表达M. mulatta CD 40和IL-10蛋白。产生的杂交瘤，人性化的筛选用这些重组非人灵长类动物蛋白免疫的小鼠与PBMC和来自恒河猴的天然蛋白的反应性。 我们还对靶向B细胞和自然杀伤（NK）细胞的单克隆抗体进行了体内评价。评估了这些候选研究试剂消耗靶向淋巴细胞亚群的能力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The in vivo administration of monoclonal antibodies that bind to cell-surface molecules can block the actions mediated by those molecules, deliver stimulatory signals through the bound molecules, or result in depletion of the targeted cell population. This approach has been extremely useful to study immunopathogenic events in rodent models. To enhance the usefulness of existing nonhuman primate models of disease, we have developed new fully human monoclonal antibodies for in vivo administration to macaque monkeys. These new antibodies were developed by cloning and expressing M. mulatta CD40 and IL-10 proteins. Resulting hybridomas from ¿humanized¿ mice immunized with these recombinant, nonhuman primate proteins were screened for reactivity with PBMC and native proteins from rhesus monkeys. We also performed in vivo evaluation of monoclonal antibodies targeting B cells and natural killer (NK) cells. The ability of these candidate research reagents to deplete the targeted lymphocyte subpopulation was assessed.