Brain pharmacokinetics of two BBB penetrating bispecific antibodies of different size.

ABSTRACT:

Background

Transferrin receptor (TfR1) mediated enhanced brain delivery of antibodies have been studied extensively in preclinical settings. However, the brain pharmacokinetics, i.e. brain entry, distribution and elimination are still not fully understood for this class of antibodies. The overall aim of the study was to compare the brain pharmacokinetics of two BBB-penetrating bispecific antibodies of different size (210 vs 58 kDa). Specifically, we wanted to investigate if the faster systemic clearance of the smaller non-IgG antibody di-scFv3D6-8D3, in comparison with the IgG-based bispecific antibody mAb3D6-scFv8D3, was also reflected in the brain.

Methods

Wild-type (C57/Bl6) mice were injected with ¹²⁵I-iodinated ([¹²⁵I]) mAb3D6-scFv8D3 (n = 46) or [

SUBMITTER: Faresjo R 

PROVIDER: S-EPMC8170802 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature