Bispecific antibody generated with sortase and click chemistry has broad antiinfluenza virus activity

通过分选酶和点击化学产生的双特异性抗体具有广泛的抗流感病毒活性

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作者:Koen Wagner, Mark J Kwakkenbos, Yvonne B Claassen, Kelly Maijoor, Martino Böhne, Koenraad F van der Sluijs, Martin D Witte, Diana J van Zoelen, Lisette A Cornelissen, Tim Beaumont, Arjen Q Bakker, Hidde L Ploegh, Hergen Spits

Abstract

Bispecific antibodies have therapeutic potential by expanding the functions of conventional antibodies. Many different formats of bispecific antibodies have meanwhile been developed. Most are genetic modifications of the antibody backbone to facilitate incorporation of two different variable domains into a single molecule. Here, we present a bispecific format where we have fused two full-sized IgG antibodies via their C termini using sortase transpeptidation and click chemistry to create a covalently linked IgG antibody heterodimer. By linking two potent anti-influenza A antibodies together, we have generated a full antibody dimer with bispecific activity that retains the activity and stability of the two fusion partners.

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