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-heavy-chain monoclonal antibodies directed to the acidic regions of the factor VIII molecule inhibit the binding of factor VIII to phospholipids and von Willebrand factor.

Recent studies have shown that inhibitors develop against acidic regions of the FVIII molecule, which contain important functional sites. However, their mechanisms of inhibition are not well understood. In this study, two anti-human FVIII mouse monoclonal antibodies (MAbs), directed towards the exposed acidic regions of the FVIII molecule, were developed, characterised and their mechanisms of inhibition investigated.

Peptide decoys selected by phage display block in vitro and in vivo activity of a human anti-FVIII inhibitor.

Hemophilia A is a life-threatening, hemorrhagic, X-linked recessive disorder resulting in deficient factor VIII (FVIII) activity. After the infusion of therapeutic FVIII, 25% of patients develop anti-FVIII antibodies that inhibit FVIII procoagulant activity, thus precluding further administration of FVIII. Here we report a novel approach aimed at neutralizing the activity of FVIII inhibitors by peptide epitope surrogates.