Characterisation and application of recombinant FVIII-neutralising antibodies from haemophilia A inhibitor patients.
antibodies
bleeding disorders
coagulation factors
factor VIII
haemophilia
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
05
08
2020
accepted:
16
10
2020
pubmed:
12
5
2021
medline:
29
9
2021
entrez:
11
5
2021
Statut:
ppublish
Résumé
The development of anti-drug antibodies (ADAs) is a serious outcome of treatment strategies involving biological medicines. Coagulation factor VIII (FVIII) is used to treat haemophilia A patients, but its immunogenicity precludes a third of severe haemophiliac patients from receiving this treatment. The availability of patient-derived anti-drug antibodies can help us better understand drug immunogenicity and identify ways to overcome it. Thus, there were two aims to this work: (i) to develop and characterise a panel of recombinant, patient-derived, monoclonal antibodies covering a range of FVIII epitopes with varying potencies, kinetics and mechanism of action, and (ii) to demonstrate their applicability to assay development, evaluation of FVIII molecules and basic research. For the first objective we used recombinant antibodies to develop a rapid, sensitive, flexible and reproducible ex vivo assay that recapitulates inhibitor patient blood using blood from healthy volunteers. We also demonstrate how the panel can provide important information about the efficacy of FVIII products and reagents without the need for patient or animal material. These materials can be used as experimental exemplars or controls, as well as tools for rational, hypothesis-driven research and assay development in relation to FVIII immunogenicity and FVIII-related products.
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Blood Coagulation Factor Inhibitors
0
Recombinant Proteins
0
F8 protein, human
839MOZ74GK
Factor VIII
9001-27-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
976-987Informations de copyright
© 2021 British Society for Haematology and John Wiley & Sons Ltd.
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