factor viii: perspectives on immunogenicity and tolerogenic strategies for hemophilia a patients

A major complication in treating hemophilia a is the development of neutralizing antibodies (inhibitors) against therapeutic administered factor viii (fviii), which occurs in approximately 20-30% of patients with severe disease. these inhibitors render fviii replacement therapy ineffective and increase the morbidity and mortality risk. the currently accepted method to eradicate inhibitors is immune tolerance induction (iti), and frequent intensive administration of fviii until inhibitor titers drop. current iti protocols are extremely costly and not effective in all patients. during the last decade, many types of research have been accomplished to clarify the mechanisms that mediate immune tolerance induction. novel experimental therapies including monoclonal antibodies, viral vector-mediated gene therapy, regulatory t cell induction using immunosuppressive drugs, and nanoparticle-based immune modulation show promising results in hemophilia a clinical trials. this review focuses on treatment options towards the anti-fviii immune responses and current novel therapies in clinical trials.