TU Darmstadt / ULB / TUbiblio

Grabbing the Bull by Both Horns: Bovine Ultralong CDR-H3 Paratopes Enable Engineering of ‘Almost Natural’ Common Light Chain Bispecific Antibodies Suitable For Effector Cell Redirection

Klewinghaus, Daniel ; Pekar, Lukas ; Arras, Paul ; Krah, Simon ; Valldorf, Bernhard ; Kolmar, Harald ; Zielonka, Stefan (2022)
Grabbing the Bull by Both Horns: Bovine Ultralong CDR-H3 Paratopes Enable Engineering of ‘Almost Natural’ Common Light Chain Bispecific Antibodies Suitable For Effector Cell Redirection.
In: Frontiers in Immunology, 12
doi: 10.3389/fimmu.2021.801368
Artikel, Bibliographie

Dies ist die neueste Version dieses Eintrags.

Kurzbeschreibung (Abstract)

A subset of antibodies found in cattle comprises ultralong CDR-H3 regions of up to 70 amino acids. Interestingly, this type of immunoglobulin usually pairs with the single germline VL gene, V30 that is typically very conserved in sequence. In this work, we have engineered ultralong CDR-H3 common light chain bispecific antibodies targeting Epidermal Growth Factor Receptor (EGFR) on tumor cells as well as Natural Cytotoxicity Receptor NKp30 on Natural Killer (NK) cells. Antigen-specific common light chain antibodies were isolated by yeast surface display by means of pairing CDR-H3 diversities following immunization with a single V30 light chain. After selection, EGFR-targeting paratopes as well as NKp30-specific binders were combined into common light chain bispecific antibodies by exploiting the strand-exchange engineered domain (SEED) technology for heavy chain heterodimerization. Biochemical characterization of resulting bispecifics revealed highly specific binding to the respective antigens as well as simultaneous binding to both targets. Most importantly, engineered cattle-derived bispecific common light chain molecules elicited potent NK cell redirection and consequently tumor cell lysis of EGFR-overexpressing cells as well as robust release of proinflammatory cytokine interferon-γ. Taken together, this data is giving clear evidence that bovine bispecific ultralong CDR-H3 common light chain antibodies are versatile for biotechnological applications.

Typ des Eintrags: Artikel
Erschienen: 2022
Autor(en): Klewinghaus, Daniel ; Pekar, Lukas ; Arras, Paul ; Krah, Simon ; Valldorf, Bernhard ; Kolmar, Harald ; Zielonka, Stefan
Art des Eintrags: Bibliographie
Titel: Grabbing the Bull by Both Horns: Bovine Ultralong CDR-H3 Paratopes Enable Engineering of ‘Almost Natural’ Common Light Chain Bispecific Antibodies Suitable For Effector Cell Redirection
Sprache: Englisch
Publikationsjahr: 2022
Verlag: Frontiers Media S.A.
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Frontiers in Immunology
Jahrgang/Volume einer Zeitschrift: 12
Kollation: 12 Seiten
DOI: 10.3389/fimmu.2021.801368
Zugehörige Links:
Kurzbeschreibung (Abstract):

A subset of antibodies found in cattle comprises ultralong CDR-H3 regions of up to 70 amino acids. Interestingly, this type of immunoglobulin usually pairs with the single germline VL gene, V30 that is typically very conserved in sequence. In this work, we have engineered ultralong CDR-H3 common light chain bispecific antibodies targeting Epidermal Growth Factor Receptor (EGFR) on tumor cells as well as Natural Cytotoxicity Receptor NKp30 on Natural Killer (NK) cells. Antigen-specific common light chain antibodies were isolated by yeast surface display by means of pairing CDR-H3 diversities following immunization with a single V30 light chain. After selection, EGFR-targeting paratopes as well as NKp30-specific binders were combined into common light chain bispecific antibodies by exploiting the strand-exchange engineered domain (SEED) technology for heavy chain heterodimerization. Biochemical characterization of resulting bispecifics revealed highly specific binding to the respective antigens as well as simultaneous binding to both targets. Most importantly, engineered cattle-derived bispecific common light chain molecules elicited potent NK cell redirection and consequently tumor cell lysis of EGFR-overexpressing cells as well as robust release of proinflammatory cytokine interferon-γ. Taken together, this data is giving clear evidence that bovine bispecific ultralong CDR-H3 common light chain antibodies are versatile for biotechnological applications.

Freie Schlagworte: bovine ultralong CDR-H3 antibodies, bispecific antibodies, effector cell redirection, NK cell engagers, common light chain, antibody engineering, yeast surface display
Sachgruppe der Dewey Dezimalklassifikatin (DDC): 500 Naturwissenschaften und Mathematik > 540 Chemie
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit
Fachbereich(e)/-gebiet(e): 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
PPN:
Export:
Suche nach Titel in: TUfind oder in Google

Verfügbare Versionen dieses Eintrags

Frage zum Eintrag Frage zum Eintrag

Optionen (nur für Redakteure)
Redaktionelle Details anzeigen Redaktionelle Details anzeigen