title: Photosensitisation facilitates cross-priming of adjuvant-free protein vaccines and stimulation of tumour-suppressing CD8 T cells.
abstract: Cancer vaccines aim to induce CD8 T cells infiltrating the tumour. For protein-based vaccines, the main biological barrier to overcome is the default MHC class-II-pathway, with activation of CD4 T cells rather than CD8 T cells. The latter requires antigens to access the cytosol and MHC class I antigen presentation. We applied photosensitiser and light to trigger disruption of antigen-containing endosomes and thereby MHC class I cross-presentation of a model cancer vaccine. This "photochemical internalisation" resulted in activation, proliferation, and IFN-γ production of cytotoxic CD8 T cells, which suppressed tumour growth by infiltrating CD8 T cells and caspase-3-dependent apoptosis. The process was independent of MHC class II, MyD88, and TLR4 signalling, but dependent on trypsin- and caspase-like proteasome activity and partly also on chloroquine. This novel method of vaccination may find applications in cancer immunotherapy where the activation of CD8 T cells is important.
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland; Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, 0310 Oslo, Norway.
authors.forename: Monika
authors.initials: M
authors.lastname: Håkerud
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, 0310 Oslo, Norway.
authors.forename: Pål K
authors.initials: PK
authors.lastname: Selbo
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
authors.forename: Ying
authors.initials: Y
authors.lastname: Waeckerle-Men
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Contassot
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Dziunycz
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kündig
authors.affiliation: PCI Biotech AS, Strandveien 55, 1366 Lysaker, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Høgset
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland. Electronic address: pal.johansen@usz.ch.
authors.forename: Pål
authors.initials: P
authors.lastname: Johansen
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D049109:Cell Proliferation; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008027:Light; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010787:Photosensitivity Disorders; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D013154:Spleen / Q000166:cytology
chemical_list: D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D017319:Photosensitizing Agents; D011166:Porphyrins; C559366:meso-tetraphenyl chlorin disulphonate; D007371:Interferon-gamma; D010047:Ovalbumin
keywords: Antigen delivery; Cancer vaccine; Cytosol targeting; Photosensitization