A pH-sensitive binding modality allows successful transferrin receptor-mediated transcytosis of a bivalent antibody across brain barriers.

ABSTRACT: Efficient delivery of therapeutics to the central nervous system (CNS) is one of the major challenges in treating neurological diseases due to brain barriers, which prevent entry of almost all potential therapeutic agents into the CNS. Targeting receptors that induce receptor-mediated transcytosis (RMT) across brain barriers has long been heralded as a potential solution to this problem, but this approach has yet to deliver clinical improvements for patients. Here, we set out to identify and characterize bivalent antibodies against the transferrin receptor 1 (TfR) as mediators of RMT. We identified the antibody YU904-F06 (hereafter referred to as F06) that showed efficient transcytosis as a bivalent IgG in two independent in vitro models of brain barriers. Despite its high affinity at extr

SUBMITTER: Kuhn P 

PROVIDER: S-EPMC12456222 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature