Generation of binder-format-payload conjugate-matrices by antibody chain-exchange.

Immunoconjugates / chemistry Humans Antibodies, Bispecific / chemistry Receptor, ErbB-2 / immunology Cell Line, Tumor Animals Trastuzumab / chemistry Haptens / chemistry Epitopes / chemistry Immunoglobulin Fc Fragments / chemistry

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
31 Oct 2024
Historique:
received: 24 06 2024
accepted: 21 10 2024
medline: 31 10 2024
pubmed: 31 10 2024
entrez: 31 10 2024
Statut: epublish

Résumé

The generation of antibody-drug conjugates with optimal functionality depends on many parameters. These include binder epitope, antibody format, linker composition, conjugation site(s), drug-to-antibody ratio, and conjugation method. The production of matrices that cover all possible parameters is a major challenge in identifying optimal antibody-drug conjugates. To address this bottleneck, we adapted our Format Chain Exchange technology (FORCE), originally established for bispecific antibodies, toward the generation of binder-format-payload matrices (pair-FORCE). Antibody derivatives with exchange-enabled Fc-heterodimers are combined with payload-conjugated Fc donors, and subsequent chain-exchange transfers payloads to antibody derivatives in different formats. The resulting binder-format-conjugate matrices can be generated with cytotoxic payloads, dyes, haptens, and large molecules, resulting in versatile tools for ADC screening campaigns. We show the relevance of pair-FORCE for identifying optimal HER2-targeting antibody-drug conjugates. Analysis of this matrix reveals that the notion of format-defines-function applies not only to bispecific antibodies, but also to antibody-drug conjugates.

Identifiants

DOI: 10.1038/s41467-024-53730-3 PMID: 39477939
pubmed: 39477939
doi: 10.1038/s41467-024-53730-3
pii: 10.1038/s41467-024-53730-3
doi:

Substances chimiques

Immunoconjugates 0
Antibodies, Bispecific 0
Receptor, ErbB-2 EC 2.7.10.1
ERBB2 protein, human EC 2.7.10.1
Trastuzumab P188ANX8CK
Haptens 0
Epitopes 0
Immunoglobulin Fc Fragments 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

9406

Informations de copyright

© 2024. The Author(s).

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Auteurs

Vedran Vasic (V)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.
ORCID: 0000-0003-2575-1006

Steffen Dickopf (S)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.
Veraxa Biotech, Heidelberg, Germany.

Nadine Spranger (N)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.
Institute of Molecular Immunology, School of Medicine and Health, Technical University Munich (TUM), Munich, Germany.

Rose-Sophie Rosenberger (RS)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.

Michaela Fischer (M)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.

Klaus Mayer (K)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.

Vincent Larraillet (V)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.

Jack A Bates (JA)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.

Verena Maier (V)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.

Tatjana Sela (T)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.

Bianca Nussbaum (B)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.

Harald Duerr (H)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.

Stefan Dengl (S)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany.

Ulrich Brinkmann (U)

Roche Pharma Research and Early Development (pRED), Large Molecule Research (LMR), Roche Innovation Center Munich, Penzberg, Germany. ulrich.brinkmann@roche.com.
ORCID: 0000-0002-5558-0212

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Facteurs immunologiques › Immunoconjugués › Generation of binder-format-payload...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Generation of binder-format-payload...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps bispécifiques › Generation of binder-format-payload...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Récepteur ErbB-2 › Generation of binder-format-payload...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Generation of binder-format-payload...
questionsmedicales.fr › Eucaryotes › Animaux › Generation of binder-format-payload...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Trastuzumab › Generation of binder-format-payload...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Épitopes › Haptènes › Generation of binder-format-payload...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Épitopes › Generation of binder-format-payload...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Fragments d'immunoglobuline › Fragments Fc des immunoglobulines › Generation of binder-format-payload...