Antidrug antibodies against the polyethylene glycol moiety inhibit the procoagulant activity of therapeutic polyethylene glycolated factor VIII.

Humans Factor VIII Polyethylene Glycols / therapeutic use Polyethylene / therapeutic use Hemophilia A / drug therapy Hemostatics / therapeutic use Immunoglobulin G Immunoglobulin A
adaptive immunity hemophilia A innate immunity neutralizing antibodies polyethylene glycol

Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
06 2023
Historique:
received: 23 09 2022
revised: 07 03 2023
accepted: 07 03 2023
medline: 15 5 2023
pubmed: 20 3 2023
entrez: 19 3 2023
Statut: ppublish

Résumé

The standard therapy for patients with hemophilia A (HA) is the replacement with factor VIII (FVIII) therapeutics. To overcome the limitation of short half-life of wild-type FVIII protein, polyethylene glycol (PEG) can be coupled to therapeutic FVIII to improve pharmacokinetics. We aimed to characterize antibodies developed against a FVIII therapeutic PEGylated with a 40-kDa PEG (40PEG-BDD An inhouse bead-based immunoassay was developed to characterize and confirm the specificity of the detected antibodies. The neutralizing nature of the antibodies toward PEGylated therapeutics was determined by a modified Nijmegen-Bethesda assay. Two out of 46 patients treated with 40PEG-BDD Antibodies against the PEG moiety of 40PEG-BDD

Sections du résumé

BACKGROUND
The standard therapy for patients with hemophilia A (HA) is the replacement with factor VIII (FVIII) therapeutics. To overcome the limitation of short half-life of wild-type FVIII protein, polyethylene glycol (PEG) can be coupled to therapeutic FVIII to improve pharmacokinetics.
OBJECTIVES
We aimed to characterize antibodies developed against a FVIII therapeutic PEGylated with a 40-kDa PEG (40PEG-BDD
METHODS
An inhouse bead-based immunoassay was developed to characterize and confirm the specificity of the detected antibodies. The neutralizing nature of the antibodies toward PEGylated therapeutics was determined by a modified Nijmegen-Bethesda assay.
RESULTS
Two out of 46 patients treated with 40PEG-BDD
CONCLUSION
Antibodies against the PEG moiety of 40PEG-BDD

Identifiants

DOI: 10.1016/j.jtha.2023.03.011 PMID: 36934798
pubmed: 36934798
pii: S1538-7836(23)00241-6
doi: 10.1016/j.jtha.2023.03.011
pii:
doi:

Substances chimiques

Factor VIII 9001-27-8
Polyethylene Glycols 3WJQ0SDW1A
Polyethylene 9002-88-4
Hemostatics 0
Immunoglobulin G 0
Immunoglobulin A 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1503-1514

Informations de copyright

Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.

Auteurs

Behnaz Pezeshkpoor (B)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany. Electronic address: behnaz.pezeshkpoor@ukbonn.de.

Nadja Sereda (N)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany.

Ann-Cristin Berkemeier (AC)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany.

Isabell Matuschek (I)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany.

Nadine Schwarz (N)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany.

Peter L Turecek (PL)

Baxalta Innovations Gesellschaft mit beschränkter Haftung (GmbH), Global Medical Affairs, Vienna, Austria.

Silvia Horneff (S)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany; Center for Rare Diseases Bonn, University Clinic Bonn, Bonn, Germany.

Claudia Klein (C)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany; Center for Rare Diseases Bonn, University Clinic Bonn, Bonn, Germany.

Georg Goldmann (G)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany; Center for Rare Diseases Bonn, University Clinic Bonn, Bonn, Germany.

Natascha Marquardt (N)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany; Center for Rare Diseases Bonn, University Clinic Bonn, Bonn, Germany.

Thilo Albert (T)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany.

Jens Müller (J)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany.

Johannes Oldenburg (J)

Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany; Center for Rare Diseases Bonn, University Clinic Bonn, Bonn, Germany.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Antidrug antibodies against the polyethylene...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Facteur VIII › Antidrug antibodies against the polyethylene...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomédicaux et dentaires › Polymères › Polyéthylène glycols › Antidrug antibodies against the polyethylene...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomédicaux et dentaires › Polymères › Matières plastiques › Polyéthylènes › Polyéthylène › Antidrug antibodies against the polyethylene...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Troubles héréditaires de la coagulation sanguine › Hémophilie A › Antidrug antibodies against the polyethylene...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents hématologiques › Coagulants › Hémostatiques › Antidrug antibodies against the polyethylene...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline G › Antidrug antibodies against the polyethylene...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline A › Antidrug antibodies against the polyethylene...