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A Generic Strategy to Generate Bifunctional Two-in-One Antibodies by Chicken Immunization

Harwardt, Julia ; Bogen, Jan P. ; Carrara, Stefania C. ; Ulitzka, Michael ; Grzeschik, Julius ; Hock, Björn ; Kolmar, Harald (2022):
A Generic Strategy to Generate Bifunctional Two-in-One Antibodies by Chicken Immunization. (Publisher's Version)
In: Frontiers in Immunology, 13, Frontiers Media S.A., e-ISSN 1664-3224,
DOI: 10.26083/tuprints-00021242,
[Article]

Abstract

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.

Item Type: Article
Erschienen: 2022
Creators: Harwardt, Julia ; Bogen, Jan P. ; Carrara, Stefania C. ; Ulitzka, Michael ; Grzeschik, Julius ; Hock, Björn ; Kolmar, Harald
Origin: Secondary publication DeepGreen
Status: Publisher's Version
Title: A Generic Strategy to Generate Bifunctional Two-in-One Antibodies by Chicken Immunization
Language: English
Abstract:

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.

Journal or Publication Title: Frontiers in Immunology
Volume of the journal: 13
Publisher: Frontiers Media S.A.
Collation: 14 Seiten
Uncontrolled Keywords: bispecific antibody, two-in-one antibody, dual action fab, yeast display, chicken-derived
Divisions: Interdisziplinäre Forschungsprojekte
Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology
07 Department of Chemistry
07 Department of Chemistry > Fachgebiet Biochemie
Date Deposited: 09 May 2022 13:53
DOI: 10.26083/tuprints-00021242
URL / URN: https://tuprints.ulb.tu-darmstadt.de/21242
URN: urn:nbn:de:tuda-tuprints-212426
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