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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.
In: Frontiers in Immunology, 13
doi: 10.3389/fimmu.2022.888838
Artikel, Bibliographie

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Kurzbeschreibung (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.

Typ des Eintrags: Artikel
Erschienen: 2022
Autor(en): Harwardt, Julia ; Bogen, Jan P. ; Carrara, Stefania C. ; Ulitzka, Michael ; Grzeschik, Julius ; Hock, Björn ; Kolmar, Harald
Art des Eintrags: Bibliographie
Titel: A Generic Strategy to Generate Bifunctional Two-in-One Antibodies by Chicken Immunization
Sprache: Englisch
Publikationsjahr: 2022
Verlag: Frontiers Media S.A.
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Frontiers in Immunology
Jahrgang/Volume einer Zeitschrift: 13
Kollation: 14 Seiten
DOI: 10.3389/fimmu.2022.888838
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Kurzbeschreibung (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.

Freie Schlagworte: bispecific antibody, two-in-one antibody, dual action fab, yeast display, chicken-derived
Sachgruppe der Dewey Dezimalklassifikatin (DDC): 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Fachbereich(e)/-gebiet(e): Interdisziplinäre Forschungsprojekte
Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology
07 Fachbereich Chemie
07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie
07 Fachbereich Chemie > Clemens-Schöpf-Institut
Hinterlegungsdatum: 02 Aug 2024 12:41
Letzte Änderung: 02 Aug 2024 12:41
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