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Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2002-06-1886. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-06-1886v1 2002-06-1886v2 102/3/949    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Villard, S. Articles by Granier, C. Search for Related Content PubMed PubMed Citation Articles by Villard, S. Articles by Granier, C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Immunotherapy Brief Reports Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2003, Vol. 102, No. 3, pp. 949-952 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report Peptide decoys selected by phage display block in vitro and in vivo activity of a human anti-FVIII inhibitor Sylvie Villard, Sébastien Lacroix-Desmazes, Thomas Kieber-Emmons, Dominique Piquer, Sabrina Grailly, Abdellah Benhida, Srini V. Kaveri, Jean-Marie Saint-Remy, and Claude Granier From the Unité Mixte de Recherche 5094 of the Centre National de la Recherche Scientifique Institut National de la Recherche Médicale, Faculté de Pharmacie, Montpellier; Institut National de la Santé et de la Recherche Médicale (INSERM) U430, Institut des Cordeliers, Paris, France; the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia; and the Center for Molecular and Vascular Biology, University of Leuven, Belgium 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. To illustrate our concept, we chose the human anti-FVIII monoclonal antibody, Bo2C11, as a representative of anti-FVIII antibodies and a phage-displayed peptide library approach to obtain surrogate peptides. We selected a series of constrained dodecapeptides with the core sequence W-NR, which specifically interacts with the combining site of Bo2C11. The peptides mimic the epitope recognized by Bo2C11 and are able to inhibit specifically and in a dose-dependent manner the binding of Bo2C11 to FVIII. Peptide 107, in particular, neutralized the activity of Bo2C11 in vitro and restored normal hemostasis in hemophilic mice. Thus, the use of peptide decoys may be a promising new approach for the neutralization of pathologic antibodies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Peptide decoys: cure for FVIII inhibitors? Alexey Khrenov and Evgueni Saenko Blood 2003 102: 777. 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