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Front Immunol. 2018 Apr 4;9:650. doi: 10.3389/fimmu.2018.00650. eCollection 2018.

Photochemical Internalization of Peptide Antigens Provides a Novel Strategy to Realize Therapeutic Cancer Vaccination.

Author information

1
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, Trondheim, Norway.
2
Centre of Molecular Inflammation Research (CEMIR), Norwegian University of Science and Technology, Trondheim, Norway.
3
Department of Infection, St. Olavs University Hospital, Trondheim, Norway.
4
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium Hospital, Oslo, Norway.
5
Department of Chemistry, Faculty of Natural Science, Norwegian University of Science and Technology, Trondheim, Norway.
6
Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo University Hospital, Oslo, Norway.
7
PCI Biotech AS, Oslo, Norway.

Abstract

Effective priming and activation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs) is crucial for realizing the potential of therapeutic cancer vaccination. This requires cytosolic antigens that feed into the MHC class I presentation pathway, which is not efficiently achieved with most current vaccination technologies. Photochemical internalization (PCI) provides an emerging technology to route endocytosed material to the cytosol of cells, based on light-induced disruption of endosomal membranes using a photosensitizing compound. Here, we investigated the potential of PCI as a novel, minimally invasive, and well-tolerated vaccination technology to induce priming of cancer-specific CTL responses to peptide antigens. We show that PCI effectively promotes delivery of peptide antigens to the cytosol of antigen-presenting cells (APCs) in vitro. This resulted in a 30-fold increase in MHC class I/peptide complex formation and surface presentation, and a subsequent 30- to 100-fold more efficient activation of antigen-specific CTLs compared to using the peptide alone. The effect was found to be highly dependent on the dose of the PCI treatment, where optimal doses promoted maturation of immature dendritic cells, thus also providing an adjuvant effect. The effect of PCI was confirmed in vivo by the successful induction of antigen-specific CTL responses to cancer antigens in C57BL/6 mice following intradermal peptide vaccination using PCI technology. We thus show new and strong evidence that PCI technology holds great potential as a novel strategy for improving the outcome of peptide vaccines aimed at triggering cancer-specific CD8+ CTL responses.

KEYWORDS:

CD8+ cytotoxic T cells; MHC class I antigen presentation; adjuvant effect; cross-presentation; peptide vaccination; photochemical internalization; photosensitizer; therapeutic tumor vaccination

PMID:
29670624
PMCID:
PMC5893651
DOI:
10.3389/fimmu.2018.00650
[Indexed for MEDLINE]
Free PMC Article

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