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 |
| Zugehörige Links: | |
| 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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| Suche nach Titel in: | TUfind oder in Google |
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- Intein mediated high throughput screening for bispecific antibodies. (deposited 19 Aug 2024 09:47) [Gegenwärtig angezeigt]
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