Characterisation and application of recombinant FVIII‐neutralising antibodies from haemophilia A inhibitor patients. (10th May 2021)

• Record Type: Journal Article
• Authors: Coxon, Carmen H.; Yu, Xinren; Beavis, James; Diaz‐Saez, Laura; Riches‐Duit, Andrew; Ball, Chris; Diamond, Scott L.; Raut, Sanj
• Is Part Of: British journal of haematology. Volume 193:Number 5(2021)
• Page Start: 976
• Page End: 987
• Publication Date: 2021-05-10
• Subjects: antibodies -- bleeding disorders -- coagulation factors -- factor VIII -- haemophilia; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.17227
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: 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.