Premium
Predictive immunogenicity of Refacto ® AF
Author(s) -
Delignat S.,
Repessé Y.,
Gilardin L.,
Dimitrov J. D.,
Lone Y.C.,
Kaveri S. V.,
LacroixDesmazes S.
Publication year - 2014
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.12348
Subject(s) - immunogenicity , medicine , food science , immunology , antigen , biology
Summary 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 CD 206, the dose‐dependent endocytosis by immature monocyte‐derived dendritic cells ( DC s), the activation by FVIII ‐loaded DC s of a FVIII ‐specific HLA ‐ DRB 1*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 DC s 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.