title: Chronic delivery of antibody fragments using immunoisolated cell implants as a passive vaccination tool.
abstract: BACKGROUND
  Monoclonal antibodies and antibody fragments are powerful biotherapeutics for various debilitating diseases. However, high production costs, functional limitations such as inadequate pharmacokinetics and tissue accessibility are the current principal disadvantages for broadening their use in clinic.
  
  
  RESULTS
  We report a novel method for the long-term delivery of antibody fragments. We designed an allogenous immunoisolated implant consisting of polymer encapsulated myoblasts engineered to chronically release scFv antibodies targeted against the N-terminus of the Aβ peptide. Following a 6-month intracerebral therapy we observed a significant reduction of the production and aggregation of the Aβ peptide in the APP23 transgenic mouse model of Alzheimer's disease. In addition, functional assessment showed prevention of behavioral deficits related to anxiety and memory traits.
  
  
  CONCLUSIONS
  The chronic local release of antibodies using immunoisolated polymer cell implants represents an alternative passive vaccination strategy in Alzheimer's disease. This novel technique could potentially benefit other diseases presently treated by local and systemic antibody administration.
authors.affiliation: Neurodegenerative Studies Laboratory, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Osiris
authors.initials: O
authors.lastname: Marroquin Belaunzaran
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Cordero
authors.forename: Veronica
authors.initials: V
authors.lastname: Setola
authors.forename: Siro
authors.initials: S
authors.lastname: Bianchi
authors.forename: Carmela
authors.initials: C
authors.lastname: Galli
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouche
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mlynarik
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Bensadoun
authors.forename: Maurizio
authors.initials: M
authors.lastname: Molinari
authors.forename: Patrick
authors.initials: P
authors.lastname: Aebischer
mesh_terms: D000818:Animals; D002460:Cell Line; D007116:Immunization, Passive; D007128:Immunoglobulin Fragments / Q000008:administration & dosage*; D051379:Mice
chemical_list: D007128:Immunoglobulin Fragments