NR ATNN
AU Feraudet,C.; Lacroux,C.; Morel,N.; Simon,S.; Volland,H.; Frobert,Y.; Creminon,C.; Andreoletti,O.; Grassi,J.
TI In vivo immunotherapeutic effect of anti-PrP monoclonal antibodies on mouse models of TSE infection: pharmacodynamic and pharmacokinetic analysis.
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Human prions, risk of blood products, and therapy HUMAN-11
PT Konferenz-Poster
AB Prion diseases are transmissible neurodegenerative disorders for which no therapeutic or prophylactic regimens exist. Passive immunization with antibodies directed against the cellular form of the prion protein (PrPc) has been shown to delay the onset of prion disease when infection occurs from periphery, but in vivo mechanisms and antibody disposition are not known so far. In the present study, we have characterized, the main lines of the pharmacokinetic properties of anti-PrP antibodies in different mouse models expressing various levels of PrPc (Prnp0/0, C57BL/6 and tga20 mice) in correlation with therapeutic effect. In agreement with our previous finding on cellular models of TSE infection, we confirm that the in vivo injection of massive amounts of anti-PrP antibodies induce a spectacular increase of circulating PrP (up to 100 fold). Together with their binding properties, pharmacokinetic characteristics of antibodies control the issue of the treatment. Therapeutic efficacy is correlated with the ability of antibodies to form long-lasting complexes with new recruited plasmatic endogenous PrP molecules. From that point of view, the situation seems to be less favourable in tga20 mice over expressing mouse PrPc because higher levels of endogenous PrPc reduce the availability of antibodies for a therapeutic effect. This study allowed us to select the anti-PrP monoclonal antibodies bearing optimal properties for passive immunotherapy and to design appropriate treatments.
AD Cécile Féraudet, Nathalie Morel, Stéphanie Simon, Hervé Volland, Yveline Frobert, Christophe Créminon, Jacques Grassi, CEA, Service de Pharmacologie et d'Immunologie, CEA/Saclay, 91191 Gif sur Yvette, France; Caroline Lacroux, Olivier Andréoletti, UMR INRA ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles 31076 Toulouse, France
SP englisch
PO Deutschland