Cattle-derived knob paratopes grafted onto peripheral loops of the IgG1 Fc region enable the generation of a novel symmetric bispecific antibody format
In this work we present a novel symmetric bispecific antibody format based on engraftments of cattle-derived knob paratopes onto peripheral loops of the IgG1 Fc region. For this, knob architectures obtained from bovine ultralong CDR-H3 antibodies were inserted into the AB loop or EF loop of the CH3...
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Published in | Frontiers in immunology Vol. 14; p. 1238313 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
24.10.2023
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Subjects | |
Online Access | Get full text |
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Summary: | In this work we present a novel symmetric bispecific antibody format based on engraftments of cattle-derived knob paratopes onto peripheral loops of the IgG1 Fc region. For this, knob architectures obtained from bovine ultralong CDR-H3 antibodies were inserted into the AB loop or EF loop of the CH3 domain, enabling the introduction of an artificial binding specificity into an IgG molecule. We demonstrate that inserted knob domains largely retain their binding affinities, resulting into bispecific antibody derivatives versatile for effector cell redirection. Essentially, generated bispecifics demonstrated adequate biophysical properties and were not compromised in their Fc mediated functionalities such as FcRn or FcγRIIIa binding. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors have contributed equally to this work and share first authorship Reviewed by: Dafne Müller, University of Stuttgart, Germany; Rajkumar Ganesan, Amgen, United States Edited by: Christian Klein, Roche Innovation Center Zurich, Switzerland |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2023.1238313 |