Binding mechanisms of therapeutic antibodies to human claudin-18.2

Cryo-EM structures of human claudin-18.2 bound to zolbetuximab and osemitamab reveal the antibody-binding mechanism, including three first extracellular loop residues critical for recognition.

• Why it matters: CLDN18.2 is normally restricted but becomes accessible on gastric tumor cells, yet high-resolution structural information on how therapeutic antibodies recognize it has been missing.
• What they did: The authors solved cryo-EM structures of hCLDN18.2 in complex with Fab fragments from zolbetuximab and osemitamab, then compared binding-relevant residues to hCLDN18.1.
• The result: Selective binding to hCLDN18.2 is structurally explained by three loop residues differing from hCLDN18.1, enabling rational design of next-generation immunotherapies targeting hCLDN18.2.

AI summary of the abstract · may contain errors · not medical advice · read the paper.