Lowering the affinity of single-chain monovalent BBB shuttle scFc-scFv8D3 prolongs its half-life and increases brain concentration.

ABSTRACT: Monoclonal antibody therapeutics is a massively growing field. Progress in providing monoclonal antibody therapeutics to treat brain disorders is complicated, due to the impermeability of the blood-brain barrier (BBB) to large macromolecular structures. To date, the most successful approach for delivering antibody therapeutics to the brain is by targeting the transferrin receptor (TfR) using anti-TfR BBB shuttles, with the 8D3 antibody being one of the most extensively studied in the field. The strategy of fine-tuning TfR binding affinity has shown promise, with previous results showing an improved brain delivery of bivalent 8D3-BBB constructs. In the current study, a fine-tuning TfR affinity strategy has been employed to improve single-chain variable fragment (scFv) 8D3 (scFv8D3) affinity

SUBMITTER: Rosa A 

PROVIDER: S-EPMC11742849 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature