Enhanced antibody half-life improves in vivo activity.
Antibodies-Monoclonal, Half-Life, Macaca-fascicularis, Mice, Mice-Inbred-C57BL, Mice-Transgenic
Nat Biotechnol 2010 Feb; 28(2):157-9.
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, J; Chamberlain, A K.; Horton, H M.; Karki, S; Leung, I W.; Sproule, T J.; Lazar, G A.; Roopenian, D C.; and Desjarlais, J R., "Enhanced antibody half-life improves in vivo activity." (2010). Faculty Research 2010. 41.