Cell-based immunotherapy of prion diseases by adoptive transfer of antigen-loaded dendritic cells or antigen-primed CD(4+) T lymphocytes.
Abstract
Prion diseases are neurodegenerative conditions caused by the transconformation of a normal host glycoprotein, the cellular prion protein (PrPc) into a neurotoxic, self-aggregating conformer (PrPSc). TSEs are ineluctably fatal and no treatment is yet available. In principle, prion diseases could be attacked from different angles including: blocking conversion of PrPc into PrPSc, accelerating the clearance of amyloid deposits in peripheral tissues and brain, stopping prion progression in secondary lymphoid organs, reducing brain inflammation and promoting neuronal healing. There are many indications that adaptive and innate immunity might mediate those effects but so far, the achievements of immunointervention have not matched all expectations. Difficulties arise from the impossibility to diagnose TSE before substantial brain damage, poor accessibility of the CNS to immunological agents, deep immune tolerance to self-PrP and short term effects of many immune interventions contrasting with the slow progression of TSEs. Here, we discuss two approaches, inspired from cancer immunotherapy, which might overcome some of those obstacles. One is vaccination with antigen-pulsed or antigen-transduced dendritic cells to bypass self-toleran...Continue Reading
References
Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy
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