title: Photochemical targeting of antigens to the cytosol for stimulation of MHC class-I-restricted T-cell responses.
abstract: Tumour chemotherapy with drugs is typically associated with severe systemic and local side effects for which reason immunotherapy represents a safer alternative. However, vaccination often fails to generate the required cytotoxic CD8 T-cell responses due to insufficient access of antigens to the cytosol and the MHC class I pathway of antigen presentation. One important issue of tumour research is therefore to develop strategies that allow cytosolic targeting or endosomal escape of tumour antigens. The objective of the current study was to test whether endocytosed antigen could be delivered to MHC class I by means of photochemical internalisation (PCI). Briefly, the antigen and the photosensitiser Amphinex were loaded in vitro onto bone-marrow-derived murine dendritic cells (DCs). After light activation, which is supposed to cause disruption of OVA- and Amphinex-containing endosomes, the DCs were cultured with OVA-specific CD8 T cells or used for immunisation of mice. PCI facilitated CD8 T-cell responses as measured by IFN-γ secretion in vitro and CD8 T-cell proliferation in vivo. In conclusion, the current proof-of-concept study is the first to describe PCI-mediated immunisation and the results revealed the feasibility of this novel technology in autologous vaccination for stimulation of CD8 T-cell responses.
authors: Department of Dermatology, University Hospital Zurich, Switzerland.
authors: Ying
authors: Y
authors: Waeckerle-Men
authors: Andrea
authors: A
authors: Mauracher
authors: Monika
authors: M
authors: Håkerud
authors: Deepa
authors: D
authors: Mohanan
authors: Thomas M
authors: TM
authors: Kündig
authors: Anders
authors: A
authors: Høgset
authors: Pål
authors: P
authors: Johansen
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000528:radiation effects; D000941:Antigens / Q000008:administration & dosage* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D002478:Cells, Cultured; D003600:Cytosol / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D004705:Endocytosis / Q000187:drug effects / Q000528:radiation effects; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D005240:Feasibility Studies; D005260:Female; D005805:Genes, MHC Class I; D007111:Immunity, Cellular / Q000187:drug effects* / Q000528:radiation effects; D007114:Immunization / Q000379:methods*; D059425:Interferon-gamma Release Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000528:radiation effects; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000941:Antigens; D017319:Photosensitizing Agents
keywords: Adjuvants; Amphinex; Antigen presentation; Apoptosis; Immunisation; Mice; Photosensitiser; T cells; Vaccines