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- Title
Predictive immunogenicity of Refacto® AF.
- Authors
DELIGNAT, S.; REPESSÉ, Y.; GILARDIN, L.; DIMITROV, J. D.; LONE, Y. C.; KAVERI, S. V.; LACROIX-DESMAZES, S.
- Abstract
The administration of therapeutic factor VIII (FVIII) to treat or prevent haemorrhages in haemophilia A patients results, in up to 30% of the cases, in the development of inhibitory anti-FVIII antibodies. Much debate has taken place on the relevance of the nature of the FVIII product as a risk factor for inhibitor development. Thus, the plasma-derived vs. recombinant origin, the second vs. third generation of the product, or the presence of the B domain have been controversially evoked. A few years ago, Refacto® AF, a third-generation recombinant B domain-deleted FVIII was marketed. The aim of this study was to compare the immunogenicity of Refacto® AF to that of two recombinant full-length FVIII products: Helixate® and Advate®. For the three recombinant FVIII products, we compared the binding to the mannose-sensitive endocytic receptor CD206, the dose-dependent endocytosis by immature monocyte-derived dendritic cells (DCs), the activation by FVIII-loaded DCs of a FVIII-specific HLA-DRB1*0101-restricted mouse T-cell hybridoma and the induction of inhibitory anti-FVIII IgG in FVIII-deficient mice. At elevated FVIII concentrations, Refacto® AF was less endocytosed than full-length recombinant products. At lower concentrations, however, Refacto® AF was endocytosed by DCs and activated T cells as well as Helixate® and Advate®. The levels of inhibitory anti-FVIII IgG induced by Refacto® AF in FVIII-deficient mice were lower or equal to that induced by Helixate® and Advate® respectively. The predicted immunogenicity of Refacto® AF is identical to or lower than that of the two recombinant full-length FVIII products available on the French market.
- Subjects
HEMOPHILIA treatment; IMMUNOGLOBULINS; HYBRIDOMAS; MANNOSE; ENDOCYTOSIS; DENDRITIC cells
- Publication
Haemophilia, 2014, Vol 20, Issue 4, p486
- ISSN
1351-8216
- Publication type
Article
- DOI
10.1111/hae.12348