Enhanced antibody half-life improves in vivo activity.
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.
Zalevsky
Jonathan
J
Xencor, Inc., Monrovia, California, USA.
Chamberlain
Aaron K
AK
Horton
Holly M
HM
Karki
Sher
S
Leung
Irene W L
IW
Sproule
Thomas J
TJ
Lazar
Greg A
GA
Roopenian
Derry C
DC
Desjarlais
John R
JR
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
D000911:Antibodies, Monoclonal