EFFECTS OF IV ADMINISTERED AMG 108 IN CHIMPANZEES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这项研究将测试一种针对白细胞介素-1受体设计的单克隆抗体。白细胞介素-1是炎症疾病的关键细胞因子，其抑制已被证明可为类风湿关节炎患者提供治疗益处。KineretTM是一种重组IL-1受体拮抗剂，目前已上市用于治疗类风湿性关节炎。AMG 108不会与任何啮齿动物或低等灵长类动物的IL-1受体发生交叉反应。为了在动物身上进行任何有意义的安全性研究，所选择的动物物种必须保持对AMG 108的生物活性。只有黑猩猩和人类对AMG 108表现出生物反应（与IL-1受体结合）。因此，黑猩猩是唯一可以在AMG 108进入人类之前用于评估其潜在毒性的灵长类动物。通过抗体抑制IL-1的作用在很大程度上是未知的，本研究的数据将有助于填补这一知识空白，并使设计更合适的临床试验成为可能。

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. This study will be testing a monoclonal antibody designed against the interleukin-1 receptor. Interleukin-1 is a key cytokine in inflammatory disorders and its inhibition has been demonstrated to provide therapeutic benefit for rheumatoid arthritis patients. As such KineretTM, a recombinant IL-1 receptor antagonist, it currently marketed for the treatment of rheumatoid arthritis. AMG 108 does not cross react with the IL-1 receptor of any rodent or lower primate species. In order for any meaningful safety studies to be carried out in animals, the animal species selected must retain biological activity against AMG 108. Only chimps and humans have demonstrated a biological response (binding to the IL-1 receptor) to AMG 108. The chimp, therefore, is the only primate species that may be used to evaluate the potential toxicity of AMG 108 prior to its introduction into humans. The effects of IL-1 inhibition through an antibody are largely unknown and data from this study will be useful in filling that knowledge gap as well as enabling the design of more appropriate clinical trials.