NR ATNO
AU Rey,C.; Knackmuss,S.; Reusch,U.; Little,M.; Weiss,S.
TI Delivery of Single chain antibodies against the prion protein receptor by passive immunotransfer and recombinant AAV as alternative approaches in TSE therapy
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-12
PT Konferenz-Poster
AB
Recently, we identified the 37/67 kDa laminin receptor (LRP/LR) as the cell surface receptor for the cellular prion protein (PrPc)1. We proved that polyclonal LRP/LR specific antibodies are able to abolish PrPsc propagation in scrapie infected neuroblastoma cells2, demonstrating that the disruption of the 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 screen of single chain antibodies (scFv) on GST::LRP by phage display. Two scFvs called N3 and S18 have been selected. We report that both scFvs recognize specifically the denatured form of LRP as well as the native form on the cell surface in BHK cells overexpressing LRP. An epitope mapping identified binding domains on LRP/LR for the antibodies. Pull-down assays revealed that these antibodies are able to interfere with the LRP-PrP interaction. The therapeutic effect of the scFvs is under investigation in the scrapie infected mouse model by passive immunization. Since infusions of antibodies 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 is based on gene therapy to specifically target the antibodies to the brain. Gene transfer via recombinant AAV vectors is a promising approach that we initiated in our laboratory.
(1) Gauczynski et al. (2001) EMBO J. 20, 5863-5875.
(2) Leucht et al. (2003) EMBO rep 4, 290-295.
AD C.Rey, S.Weiss, Genzentrum-Institut für Biochemie der LMU München, Feodor-Lynen-Str. 25; S.Knackmuss, U.Reusch, M.Little, Affimed Therapeutics AG-Technologiepark- Im Neuheimer Feld 582, 69120 Heidelberg, Germany
SP englisch
PO Deutschland