Bovine ultralong CDR-H3 derived knob paratopes elicit potent TNF- α neutralization and enable the generation of novel adalimumab-based antibody architectures with augmented features

Biol Chem. 2024 Feb 20. doi: 10.1515/hsz-2023-0370. Online ahead of print.ABSTRACTIn this work we have generated cattle-derived chimeric ultralong CDR-H3 antibodies targeting tumor necrosis factor α (TNF-α) via immunization and yeast surface display. We identified one particular ultralong CDR-H3 paratope that potently neutralized TNF-α. Interestingly, grafting of the knob architecture onto a peripheral loop of the CH3 domain of the Fc part of an IgG1 resulted in the generation of a TNF-α neutralizing Fc (Fcknob) that did not show any potency loss compared with the parental chimeric IgG format. Eventually, grafting this knob onto the CH3 region of adalimumab enabled the engineering of a novel TNF-α targeting antibody architecture displaying augmented TNF-α inhibition.PMID:38373142 | DOI:10.1515/hsz-2023-0370

Source: Biological Chemistry - February 19, 2024 Category: Chemistry Authors: Paul Arras Jasmin Zimmermann Britta Lipinski Bernhard Valldorf Andreas Evers Desislava Elter Simon Krah Achim Doerner Enrico Guarnera Vanessa Siegmund Harald Kolmar Lukas Pekar Stefan Zielonka Source Type: research