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

Cell Chem Biol. 2023-10; 
Ghasidit Pornnoppadol, Layne G Bond, Michael J Lucas, Jennifer M Zupancic, Yun-Huai Kuo, Boya Zhang, Colin F Greineder, Peter M Tessier
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摘要

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-liv... More

关键词

4F2, BBB, BDNF, SLC3A2, TrkB, astrocyte, blood-brain barrier, neuron, neurotrophin, transferrin receptor
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