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, 2022, 13
doi: 10.26083/tuprints-00021242
Artikel, Zweitveröffentlichung, Verlagsversion
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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: | Zweitveröffentlichung |
| Titel: | A Generic Strategy to Generate Bifunctional Two-in-One Antibodies by Chicken Immunization |
| Sprache: | Englisch |
| Publikationsjahr: | 2022 |
| Publikationsdatum der Erstveröffentlichung: | 2022 |
| Verlag: | Frontiers Media S.A. |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Frontiers in Immunology |
| Jahrgang/Volume einer Zeitschrift: | 13 |
| Kollation: | 14 Seiten |
| DOI: | 10.26083/tuprints-00021242 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/21242 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| 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 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-212426 |
| 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: | 09 Mai 2022 13:53 |
| Letzte Änderung: | 02 Aug 2024 12:41 |
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| Suche nach Titel in: | TUfind oder in Google |
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- A Generic Strategy to Generate Bifunctional Two-in-One Antibodies by Chicken Immunization. (deposited 09 Mai 2022 13:53) [Gegenwärtig angezeigt]
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