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Prepublished online as a Blood First Edition Paper on April 3, 2003May 1, 2003; DOI 10.1182/blood-2002-06-1886. This Article 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 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 Related Article in Blood Online Social Bookmarking                   What's this? Submitted June 26, 2002 Accepted March 25, 2003 Peptide decoys selected by phage display block in vitro and in vivo activity of a human anti-FVIII inhibitor Sylvie Villard*, Sebastien Lacroix-Desmazes, Thomas Kieber-Emmons, Dominique Piquer, Sabrina Grailly, Abdellah Benhida, Srini V Kaveri, Jean-Marie Saint-Remy, and Claude Granier Faculty of Pharmacie, UMR-CNRS 5094, Montpellier, France Institut des Cordeliers, INSERM U430, Paris, France University of Pennsylvania, Department of pathology and Lab Medecine, Philadelphia, PA, USA University of Leuven, Center for Molecular and Vascular Biology, Leuven, Belgium * Corresponding author; email: sylvie.villard{at}ibph.pharma.univ-montp1.fr. Hemophilia A is a life-threatening, hemorrhagic, X-linked recessive disorder resulting in deficient factor VIII (FVIII) activity. Following infusion of therapeutic FVIII, 25% of the 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, that 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 pathological 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. [Full Text] [PDF] This article has been cited by other articles: S. Planque, M. A. Escobar, K. C. Smith, H. Taguchi, Y. Nishiyama, E. Donnachie, K. P. Pratt, and S. Paul Covalent Inactivation of Factor VIII Antibodies from Hemophilia A Patients by an Electrophilic FVIII Analog J. Biol. Chem., May 2, 2008; 283(18): 11876 - 11886. [Abstract] [Full Text] [PDF] I. Mayrose, O. Penn, E. Erez, N. D. Rubinstein, T. Shlomi, N. T. Freund, E. M. Bublil, E. Ruppin, R. Sharan, J. M. Gershoni, et al. Pepitope: epitope mapping from affinity-selected peptides Bioinformatics, December 1, 2007; 23(23): 3244 - 3246. [Abstract] [Full Text] [PDF] I. Mayrose, T. Shlomi, N. D. Rubinstein, J. M. Gershoni, E. Ruppin, R. Sharan, and T. Pupko Epitope mapping using combinatorial phage-display libraries: a graph-based algorithm Nucleic Acids Res., January 12, 2007; 35(1): 69 - 78. [Abstract] [Full Text] [PDF] E. M. Bublil, S. Yeger-Azuz, and J. M. Gershoni Computational prediction of the cross-reactive neutralizing epitope corresponding to the monoclonal antibody b12 specific for HIV-1 gp120 FASEB J, September 1, 2006; 20(11): 1762 - 1774. [Abstract] [Full Text] [PDF] S. Lacroix-Desmazes, B. Wootla, S. Dasgupta, S. Delignat, J. Bayry, J. Reinbolt, J. Hoebeke, E. Saenko, M. D. Kazatchkine, A. Friboulet, et al. Catalytic IgG from Patients with Hemophilia A Inactivate Therapeutic Factor VIII J. Immunol., July 15, 2006; 177(2): 1355 - 1363. [Abstract] [Full Text] [PDF] V. Moreau, C. Granier, S. Villard, D. Laune, and F. Molina Discontinuous epitope prediction based on mimotope analysis Bioinformatics, May 1, 2006; 22(9): 1088 - 1095. [Abstract] [Full Text] [PDF] T. C. Lei and D. W. Scott Induction of tolerance to factor VIII inhibitors by gene therapy with immunodominant A2 and C2 domains presented by B cells as Ig fusion proteins Blood, June 15, 2005; 105(12): 4865 - 4870. [Abstract] [Full Text] [PDF]

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