Enhanced antibody half-life improves in vivo activity.

Zalevsky, Jonathan; Chamberlain, Aaron K; Horton, Holly M; Karki, Sher; Leung, Irene W L; Sproule, Thomas J; Lazar, Greg A; Roopenian, Derry C et al. · Nat Biotechnol · 2010

basic_science · Level V

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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.

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