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Intein mediated high throughput screening for bispecific antibodies

Hofmann, Tim ; Schmidt, Johannes ; Ciesielski, Elke ; Becker, Stefan ; Rysiok, Thomas ; Schütte, Mark ; Toleikis, Lars ; Kolmar, Harald ; Doerner, Achim (2024)
Intein mediated high throughput screening for bispecific antibodies.
In: mAbs, 2020, 12 (1)
doi: 10.26083/tuprints-00027688
Artikel, Zweitveröffentlichung, Verlagsversion

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Kurzbeschreibung (Abstract)

Bispecific antibodies comprise extremely diverse architectures enabling complex modes of action, such as effector cell recruitment or conditional target modulation via dual targeting, not conveyed by monospecific antibodies. In recent years, research on bispecific therapeutics has substantially grown. However, evaluation of binding moiety combinations often leads to undesired prolonged development times. While high throughput screening for small molecules and classical antibodies has evolved into a mature discipline in the pharmaceutical industry, dual-targeting antibody screening methodologies lack the ability to fully evaluate the tremendous number of possible combinations and cover only a limited portion of the combinatorial screening space. Here, we propose a novel combinatorial screening approach for bispecific IgG-like antibodies to extenuate screening limitations in industrial scale, expanding the limiting screening space. Harnessing the ability of a protein trans-splicing reaction by the split intein Npu DnaE, antibody fragments were reconstituted within the hinge region in vitro. This method allows for fully automated, rapid one-pot antibody reconstitution, providing biological activity in several biochemical and functional assays. The technology presented here is suitable for automated functional and combinatorial high throughput screening of bispecific antibodies.

Typ des Eintrags: Artikel
Erschienen: 2024
Autor(en): Hofmann, Tim ; Schmidt, Johannes ; Ciesielski, Elke ; Becker, Stefan ; Rysiok, Thomas ; Schütte, Mark ; Toleikis, Lars ; Kolmar, Harald ; Doerner, Achim
Art des Eintrags: Zweitveröffentlichung
Titel: Intein mediated high throughput screening for bispecific antibodies
Sprache: Englisch
Publikationsjahr: 19 August 2024
Ort: Darmstadt
Publikationsdatum der Erstveröffentlichung: 2020
Ort der Erstveröffentlichung: London
Verlag: Taylor & Francis
Titel der Zeitschrift, Zeitung oder Schriftenreihe: mAbs
Jahrgang/Volume einer Zeitschrift: 12
(Heft-)Nummer: 1
Kollation: 15 Seiten
DOI: 10.26083/tuprints-00027688
URL / URN: https://tuprints.ulb.tu-darmstadt.de/27688
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Herkunft: Zweitveröffentlichungsservice
Kurzbeschreibung (Abstract):

Bispecific antibodies comprise extremely diverse architectures enabling complex modes of action, such as effector cell recruitment or conditional target modulation via dual targeting, not conveyed by monospecific antibodies. In recent years, research on bispecific therapeutics has substantially grown. However, evaluation of binding moiety combinations often leads to undesired prolonged development times. While high throughput screening for small molecules and classical antibodies has evolved into a mature discipline in the pharmaceutical industry, dual-targeting antibody screening methodologies lack the ability to fully evaluate the tremendous number of possible combinations and cover only a limited portion of the combinatorial screening space. Here, we propose a novel combinatorial screening approach for bispecific IgG-like antibodies to extenuate screening limitations in industrial scale, expanding the limiting screening space. Harnessing the ability of a protein trans-splicing reaction by the split intein Npu DnaE, antibody fragments were reconstituted within the hinge region in vitro. This method allows for fully automated, rapid one-pot antibody reconstitution, providing biological activity in several biochemical and functional assays. The technology presented here is suitable for automated functional and combinatorial high throughput screening of bispecific antibodies.

Freie Schlagworte: High throughput Screening, antibody, bispecific antibody, antibody discovery, split inteins, automation
Status: Verlagsversion
URN: urn:nbn:de:tuda-tuprints-276884
Sachgruppe der Dewey Dezimalklassifikatin (DDC): 500 Naturwissenschaften und Mathematik > 540 Chemie
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Fachbereich(e)/-gebiet(e): 07 Fachbereich Chemie
07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie
07 Fachbereich Chemie > Clemens-Schöpf-Institut
Hinterlegungsdatum: 19 Aug 2024 09:47
Letzte Änderung: 20 Aug 2024 06:23
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