Bispecific antibody shuttles targeting CD98hc mediate efficient and long-lived brain delivery of IgGs.

ABSTRACT: The inability of antibodies to penetrate the blood-brain barrier (BBB) is a key limitation to their use in diverse applications. One promising strategy is to deliver IgGs using a bispecific BBB shuttle, which involves fusing an IgG to a second affinity ligand that engages a cerebrovascular endothelial target and facilitates transport across the BBB. Nearly all prior efforts have focused on shuttles that target transferrin receptor (TfR-1) despite inherent delivery and safety challenges. Here, we report bispecific antibody shuttles that engage CD98hc, the heavy chain of the large neutral amino acid transporter (LAT1), and efficiently transport IgGs into the brain. Notably, CD98hc shuttles lead to much longer-lived brain retention of IgGs than TfR-1 shuttles while enabling more specific targ

SUBMITTER: Pornnoppadol G 

PROVIDER: S-EPMC10922565 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature