A Generic Strategy to Generate Bifunctional Two-in-One Antibodies by Chicken Immunization
Various formats of bispecific antibodies exist, among them Two-in-One antibodies in which each Fab arm can bind to two different antigens. Their IgG-like architecture accounts for low immunogenicity and also circumvents laborious engineering and purification steps to facilitate correct chain pairing...
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Published in | Frontiers in immunology Vol. 13; p. 888838 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
11.04.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Various formats of bispecific antibodies exist, among them Two-in-One antibodies in which each Fab arm can bind to two different antigens. Their IgG-like architecture accounts for low immunogenicity and also circumvents laborious engineering and purification steps to facilitate correct chain pairing. Here we report for the first time the identification of a Two-in-One antibody by yeast surface display (YSD) screening of chicken-derived immune libraries. The resulting antibody simultaneously targets the epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1) at the same Fv fragment with two non-overlapping paratopes. The dual action Fab is capable of inhibiting EGFR signaling by binding to dimerization domain II as well as blocking the PD-1/PD-L1 interaction. Furthermore, the Two-in-One antibody demonstrates specific cellular binding properties on EGFR/PD-L1 double positive tumor cells. The presented strategy relies solely on screening of combinational immune-libraries and obviates the need for any additional CDR engineering as described in previous reports. Therefore, this study paves the way for further development of therapeutic antibodies derived from avian immunization with novel and tailor-made binding properties. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Ulrich Brinkmann, Roche, United Kingdom; Chang-Han Lee, Seoul National University, South Korea These authors contributed equally to this work Edited by: Christian Klein, Roche Innovation Center Zurich, Switzerland This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2022.888838 |