Generation of glycan-specific nanobodies.

Antibodies Fucose Humans Immunization Polysaccharides Single-Domain Antibodies / chemistry
Globo-H active immunization alpaca cancer glycan glycoconjugate heavy chain-only antibody immunization nanobody single-domain antibody tumor-associated carbohydrate antigen

Journal

Cell chemical biology
ISSN: 2451-9448
Titre abrégé: Cell Chem Biol
Pays: United States
ID NLM: 101676030

Informations de publication

Date de publication:
18 08 2022
Historique:
received: 26 04 2021
revised: 21 02 2022
accepted: 23 05 2022
pubmed: 16 6 2022
medline: 24 8 2022
entrez: 15 6 2022
Statut: ppublish

Résumé

The development of antibodies that target specific glycan structures on cancer cells or human pathogens poses a significant challenge due to the immense complexity of naturally occurring glycans. Automated glycan assembly enables the production of structurally homogeneous glycans in amounts that are difficult to derive from natural sources. Nanobodies (Nbs) are the smallest antigen-binding domains of heavy-chain-only antibodies (hcAbs) found in camelids. To date, the development of glycan-specific Nbs using synthetic glycans has not been reported. Here, we use defined synthetic glycans for alpaca immunization to elicit glycan-specific hcAbs, and describe the identification, isolation, and production of a Nb specific for the tumor-associated carbohydrate antigen Globo-H. The Nb binds the terminal fucose of Globo-H and recognizes synthetic Globo-H in solution and native Globo-H on breast cancer cells with high specificity. These results demonstrate the potential of our approach for generating glycan-targeting Nbs to be used in biomedical and biotechnological applications.

Identifiants

DOI: 10.1016/j.chembiol.2022.05.007 PMID: 35705094
pubmed: 35705094
pii: S2451-9456(22)00199-4
doi: 10.1016/j.chembiol.2022.05.007
pii:
doi:

Substances chimiques

Antibodies 0
Polysaccharides 0
Single-Domain Antibodies 0
Fucose 28RYY2IV3F

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1353-1361.e6

Subventions

Organisme : Wellcome Trust
ID : 203149
Pays : United Kingdom

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declarations of interests O.M. and P.H.S. are co-founders of Tacalyx GmbH, where P.H.S. is a board member. O.M. and P.H.S. have a significant financial interest in the company and field a patent for the Nbs described in this manuscript (EP3799881A1).

Auteurs

Sana Khan Khilji (SK)

Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.

Felix Goerdeler (F)

Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.

Kristin Frensemeier (K)

Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.

David Warschkau (D)

Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.

Jost Lühle (J)

Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.

Zeinab Fandi (Z)

Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Department of Life Sciences and Technology, Beuth University of Applied Sciences Berlin, 13347 Berlin, Germany.

Falko Schirmeister (F)

Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany.

Zhuo Angel Chen (ZA)

Technische Universität Berlin, Chair of Bioanalytics, 10623 Berlin, Germany.

Onur Turak (O)

Institute of Chemistry and Metabolomics, Center of Structural and Cell Biology in Medicine (CSCM), University of Lübeck, 23562 Lübeck, Germany.

Alvaro Mallagaray (A)

Institute of Chemistry and Metabolomics, Center of Structural and Cell Biology in Medicine (CSCM), University of Lübeck, 23562 Lübeck, Germany.

Stefan Boerno (S)

Sequencing Core Facility, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.

Bernd Timmermann (B)

Sequencing Core Facility, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.

Juri Rappsilber (J)

Technische Universität Berlin, Chair of Bioanalytics, 10623 Berlin, Germany; Wellcome Centre for Cell Biology, University of Edinburgh, EH9 3BF Edinburgh, UK.

Peter H Seeberger (PH)

Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany. Electronic address: peter.seeberger@mpikg.mpg.de.

Oren Moscovitz (O)

Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany. Electronic address: oren.moscovitz@mpikg.mpg.de.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Generation of glycan-specific nanobodies.
questionsmedicales.fr › Glucides › Désoses › Fucose › Generation of glycan-specific nanobodies.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Generation of glycan-specific nanobodies.
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pratiques en santé publique › Prévention primaire › Immunisation › Generation of glycan-specific nanobodies.
questionsmedicales.fr › Glucides › Polyosides › Generation of glycan-specific nanobodies.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Fragments d'immunoglobuline › Fragments Fab d'immunoglobuline › Anticorps à domaine unique › Generation of glycan-specific nanobodies.