Title

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

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.