Development of Fully Human CD98hc Antibodies to Enhance Delivery of Therapeutic Drugs Across the Blood-Brain Barrier

CD98 heavy chain (CD98hc, also known as SLC3A2), is a type II transmembrane glycoprotein that serves as a critical component of heteromeric amino acid (AA) transporters through its interaction with different light-chain partners. CD98hc is highly expressed in the blood-brain barrier (BBB), where it facilitates receptor-mediated transcytosis and has emerged as a promising target for enhancing dug delivery across the BBB.
In this study, we screened a panel of fully human CD98hc antibodies generated from NeoMab™ transgenic mice. Lead candidates demonstrated robust endocytosis and transcytosis activity in vitro without altering CD98hc receptor abundance or amino acid transport function. These findings highlight fully human CD98hc antibodies as promising transcytosis-enabling modules (TEMs) for shuttling therapeutic agents across the BBB.