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Photosensitisation facilitates cross-priming of adjuvant-free protein vaccines and stimulation of tumour-suppressing CD8 T cells.
Journal article

Photosensitisation facilitates cross-priming of adjuvant-free protein vaccines and stimulation of tumour-suppressing CD8 T cells.

  • Håkerud M 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.
  • Selbo PK Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, 0310 Oslo, Norway.
  • Waeckerle-Men Y Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
  • Contassot E Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
  • Dziunycz P Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
  • Kündig TM Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
  • Høgset A PCI Biotech AS, Strandveien 55, 1366 Lysaker, Norway.
  • Johansen P Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland. Electronic address: pal.johansen@usz.ch.
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  • 2014-12-09
Published in:
  • Journal of controlled release : official journal of the Controlled Release Society. - 2015
Antigen delivery
Cancer vaccine
Cytosol targeting
Photosensitization
Animals
CD8-Positive T-Lymphocytes
Cancer Vaccines
Cell Proliferation
Cross-Priming
Dendritic Cells
Histocompatibility Antigens Class I
Interferon-gamma
Light
Melanoma
Mice, Inbred C57BL
Mice, Transgenic
Ovalbumin
Photosensitivity Disorders
Photosensitizing Agents
Porphyrins
Skin Neoplasms
Spleen
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/298205
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