增强抗体半衰期可提高体内活性。
Enhanced antibody half-life improves in vivo activity.
机构信息
Xencor, Inc., Monrovia, California, USA.
出版信息
Nat Biotechnol. 2010 Feb;28(2):157-9. doi: 10.1038/nbt.1601. Epub 2010 Jan 17.
Abstract
Improved affinity for the neonatal Fc receptor (FcRn) is known to extend antibody half-life in vivo. However, this has never been linked with enhanced therapeutic efficacy. We tested whether antibodies with half-lives extended up to fivefold in human (h)FcRn transgenic mice and threefold in cynomolgus monkeys retain efficacy at longer dosing intervals. We observed that prolonged exposure due to FcRn-mediated enhancement of half-life improved antitumor activity of Fc-engineered antibodies in an hFcRn/Rag1(-/-) mouse model. This bridges the demand for dosing convenience with the clinical necessity of maintaining efficacy.
摘要
已知提高对新生儿 Fc 受体 (FcRn) 的亲和力可延长体内抗体的半衰期。但是，这从未与增强的治疗效果联系起来。我们测试了半衰期在 hFcRn 转基因小鼠中延长至五倍，在食蟹猴中延长至三倍的抗体是否在更长的给药间隔内保持疗效。我们观察到，由于 FcRn 介导的半衰期延长而导致的延长暴露时间可提高 Fc 工程化抗体在 hFcRn/Rag1(-/-) 小鼠模型中的抗肿瘤活性。这满足了方便给药的需求和维持疗效的临床必要性。
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