Enhanced antibody half-life improves in vivo activity.
Document Type
Article
Publication Date
2010
Keywords
Antibodies-Monoclonal, Half-Life, Macaca-fascicularis, Mice, Mice-Inbred-C57BL, Mice-Transgenic
First Page
157
Last Page
159
JAX Source
Nat Biotechnol 2010 Feb; 28(2):157-9.
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.
Recommended Citation
Zalevsky J,
Chamberlain AK,
Horton HM,
Karki S,
Leung IW,
Sproule TJ,
Lazar GA,
Roopenian DC,
Desjarlais JR.
Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 2010 Feb; 28(2):157-9.