Abstract
Monoclonal antibodies (mAbs) represent an important class of therapeutic modalities. In order to optimize their pharmaceutical properties, studies have focused on improving mAb pharmacokinetic/pharmacodynamics (PK/PD) 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 beginning to become increasingly evident that along with FcRn interactions the consideration of the non-FcRn based biological processes active in mAb disposition should be integrated into mAb development/optimization. Herein, we describe how the pharmacokinetics of mAbs can be modulated through FcRn interactions and provide perspectives on interpreting the receptor binding parameters with other mechanisms involved in antibody disposition to aid in guiding mAb development.
- biologics/therapeutic proteins
- cellular trafficking/localization
- drug clearance
- drug disposition
- pharmacokinetics
- The American Society for Pharmacology and Experimental Therapeutics