Regular Article THROMBOSIS AND HEMOSTASIS A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models
نویسندگان
چکیده
Henning R. Stennicke, Marianne Kjalke, Ditte M. Karpf, Kristoffer W. Balling, Peter B. Johansen, Torben Elm, Kristine Øvlisen, Flemming Möller, Heidi L. Holmberg, Charlotte N. Gudme, Egon Persson, Ida Hilden, Hermann Pelzer, Henrik Rahbek-Nielsen, Christina Jespersgaard, Are Bogsnes, Anette A. Pedersen, Anne K. Kristensen, Bernd Peschke, Wendy Kappers, Frederik Rode, Lars Thim, Mikael Tranholm, Mirella Ezban, Eva H. N. Olsen, and Søren E. Bjørn
منابع مشابه
THROMBOSIS AND HEMOSTASIS Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment
A long-acting factor VIII (FVIII) as a replacement therapy for hemophilia A would significantly improve treatment options for patients with hemophilia A. To develop a FVIII with an extended circulating half-life, but without a reduction in activity, we have engineered 23 FVIII variants with introduced surface-exposed cysteines to which a polyethylene glycol (PEG) polymer was specifically conjug...
متن کاملRegular Article THROMBOSIS AND HEMOSTASIS High-resolution mapping of epitopes on the C2 domain of factor VIII by analysis of point mutants using surface plasmon resonance
• Amino acid residues comprising B-cell epitopes recognized by neutralizing antifactor VIII antibodies (inhibitors) have been identified. • Amino acids contributing significant antigen–antibody binding avidity are candidates for mutagenesis in the design of less antigenic proteins. Neutralizing anti-factor VIII (FVIII) antibodies that develop in patients with hemophilia A and inmurinehemophilia...
متن کاملHEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Antithrombotic effects of controlled inhibition of factor VIII with a partially inhibitory human monoclonal antibody in a murine vena cava thrombosis model
The human monoclonal antibody mAbLE2E9 partially inactivates human factor VIII (FVIII), leaving approximately 10% residual activity. The antithrombotic efficacy of the antibody was evaluated in mouse models of inferior vena cava thrombosis. Thrombi were induced in wild-type mice given either the antibody or saline. No thrombi occurred in any of 8 mice treated with mAb-LE2E9, whereas 6 of 8 cont...
متن کاملHigh expression reduces an antibody response after neonatal gene therapy with B domain-deleted human factor VIII in mice.
BACKGROUND Gene therapy could prevent bleeding in patients with hemophilia A, but might induce antibodies that block factor VIII (FVIII) function. OBJECTIVES To test the efficacy of gene therapy in the newborn period for preventing a response to human FVIII (hFVIII) because of immaturity of the immune system. METHODS Varying doses of a retroviral vector (RV) expressing a B domain-deleted hF...
متن کاملHEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY In vivo neutralization of a C2 domain–specific human anti–Factor VIII inhibitor by an anti-idiotypic antibody
Factor VIII (FVIII) administration elicits specific inhibitory antibodies (Abs) in about 25% of patients with hemophilia A. The majority of such Abs reacts with FVIII C2 domain. mAbBO2C11 is a high-affinity human monoclonal antibody (mAb) directed toward the C2 domain, which is representative of a major class of human FVIII inhibitors. Anti-idiotypic Abs were raised to mAbBO2C11 to establish th...
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