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

J Control Release. 2015 Jan 28:198:10-7. doi: 10.1016/j.jconrel.2014.11.032. Epub 2014 Dec 4.

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.

Keywords: Antigen delivery; Cancer vaccine; Cytosol targeting; Photosensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines*
  • Cell Proliferation
  • Cross-Priming
  • Dendritic Cells / immunology
  • Histocompatibility Antigens Class I / immunology
  • Interferon-gamma / immunology
  • Light
  • Melanoma / immunology
  • Melanoma / therapy*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Photosensitivity Disorders
  • Photosensitizing Agents / therapeutic use*
  • Porphyrins / therapeutic use*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy*
  • Spleen / cytology

Substances

  • Cancer Vaccines
  • Histocompatibility Antigens Class I
  • Photosensitizing Agents
  • Porphyrins
  • meso-tetraphenyl chlorin disulphonate
  • Interferon-gamma
  • Ovalbumin