title: Enhanced antibody half-life improves in vivo activity.
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.
authors.affiliation: Xencor, Inc., Monrovia, California, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zalevsky
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Chamberlain
authors.forename: Holly M
authors.initials: HM
authors.lastname: Horton
authors.forename: Sher
authors.initials: S
authors.lastname: Karki
authors.forename: Irene W L
authors.initials: IW
authors.lastname: Leung
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sproule
authors.forename: Greg A
authors.initials: GA
authors.lastname: Lazar
authors.forename: Derry C
authors.initials: DC
authors.lastname: Roopenian
authors.forename: John R
authors.initials: JR
authors.lastname: Desjarlais
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D006207:Half-Life; D008252:Macaca fascicularis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D000911:Antibodies, Monoclonal