RT Journal Article
SR Electronic
T1 Application of FcRn Binding Assays to Guide mAb Development
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1867
OP 1872
DO 10.1124/dmd.114.059089
VO 42
IS 11
A1 Amita Datta-Mannan
A1 Victor J. Wroblewski
YR 2014
UL http://dmd.aspetjournals.org/content/42/11/1867.abstract
AB Monoclonal antibodies (mAbs) represent an important class of therapeutic modalities. To optimize their pharmaceutical properties, studies have focused on improving mAb pharmacokinetic/pharmacodynamic profiles by modulating their interactions with the neonatal Fc receptor (FcRn). The influence of both the chemical and physical properties of IgGs has been examined in the context of FcRn interactions. In this regard, a variety of FcRn binding assays and tools have been developed and used to characterize the interaction with IgGs. However, a predictive relationship between the FcRn binding interaction of IgGs in vitro and their pharmacokinetics in vivo broadly across mAbs remains elusive. Many studies have increasingly suggested that the interplay between the characteristics of the mAb and the nature of its target can influence disposition and elimination. Thus, it is becoming increasingly evident that along with FcRn interactions, consideration of the non–FcRn-based biologic processes active in mAb disposition should be integrated into mAb development and optimization. Herein, we describe how the pharmacokinetics of mAbs can be modulated through FcRn interactions and provide perspectives on interpreting the receptor binding parameters in relation to other mechanisms involved in antibody disposition to aid in guiding mAb development.