Brain pharmacokinetics of anti-transferrin receptor antibody affinity variants in rats determined using microdialysis.

ABSTRACT: Receptor-mediated transcytosis (RMT) is used to enhance the delivery of monoclonal antibodies (mAb) into the central nervous system (CNS). While the binding to endogenous receptors on the brain capillary endothelial cells (BCECs) may facilitate the uptake of mAbs in the brain, a strong affinity for the receptor may hinder the efficiency of transcytosis. To quantitatively investigate the effect of binding affinity on the pharmacokinetics (PK) of anti-transferrin receptor (TfR) mAbs in different regions of the rat brain, we conducted a microdialysis study to directly measure the concentration of free mAbs at different sites of interest. Our results confirmed that bivalent anti-TfR mAb with an optimal dissociation constant (K_D) value (76 nM) among four affinity variants can have up

SUBMITTER: Chang HY 

PROVIDER: S-EPMC7849817 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature