A shorter linker in the bispecific antibody RmAb158-scFv8D3 improves TfR-mediated blood-brain barrier transcytosis in vitro.

ABSTRACT: Transferrin Receptor (TfR)-mediated transcytosis across the blood-brain barrier (BBB) enables the uptake of bispecific therapeutic antibodies into the brain. At therapeutically relevant concentrations, bivalent binding to TfR appears to reduce the transcytosis efficiency by receptor crosslinking. In this study, we aimed to improve BBB transcytosis of symmetric antibodies through minimizing their ability to cause TfR crosslinking. We created variants of the previously published RmAb158-scFv8D3, where the linker length between RmAb158 and the mTfR-targeting scFv8D3 was adjusted. We investigated the effect of the linker length on the antibodies' binding kinetics to mTfR using ELISA and LigandTracer assays, and their ability to transcytose across BBB endothelial cells (In-Cell BBB-Trans assay)

SUBMITTER: Petersen I 

PROVIDER: S-EPMC11666562 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature