NR AOYD
AU Rey,C.; Knackmuss,S.; Reusch,U.; Roettgen,P.; Little,M.; Weiss,S.
TI Single chain antibodies as a tool for therapy in prion diseases
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - IV-25
PT Konferenz-Poster
AB
Recently, we identified the 37/67 kDa laminin receptor (LRP/LR)(1) as the cell surface receptor and HSPGs as co-factors/co-receptors (2) for the cellular prion protein (PrPc). We proved that a polyclonal LRP/LR specific antibody is able to abolish PrPsc propagation in scrapie infected neuroblastoma cells(3), demonstrating that the disruption of LRP-PrP interaction is a relevant strategy to treat prion diseases. In the aim to develop anti-TSE therapies based on antibodies, we performed a screening of single chain antibody (scFv) on GST::LRP by phage display. Two scFv called N3 and S18 have been selected. We report that both scFvs recognize specifically LRP by Western Blotting as well as the native form on the cell surface in BHK cells overexpressing LRP. Next we would like to investigate the therapeutic effect of the scFvs both in vitro in scrapie propagating cells and in vivo in scrapie mouse models. Since passive antibody transfer on the long term might lead to strong side effects and due to the fact that only a few amounts of antibodies might pass through the blood brain barrier, an alternative approach for antibody delivery represent the development of gene therapy which specifically target the antibodies to the brain. Promising approaches include (I) gene transfer via recombinant AAV vectors and (II) grafting of encapsulated antibody producing cells into the brain.
(1)Gauczynski et al., EMBO J. ,2001, 20, 5863-75
(2)Hundt et al., EMBO J., 2001, 20, 5876-86
(3)Leucht et al., EMBO rep., 2003, 4, 290-295
AD C. Rey, S. Weiss, Laboratorium für Molekulare Biologie-Genzentrum Institut für Biochemie der LMU München, Germany; S. Knackmuss, U. Reusch, P. Roettgen, M. Little, Affimed Therapeutics AG Heidelberg, Germany
SP englisch
PO Deutschland