title: Intradermal photosensitisation facilitates stimulation of MHC class-I restricted CD8 T-cell responses of co-administered antigen.
abstract: The protection or treatment of several immunological disorders is dependent on the antigen-specific and cytotoxic CD8 T cells. However, vaccines aimed at stimulating CD8 T-cell responses are typically ineffective because vaccine antigens are primarily processed by the MHC class-II and not the MHC class-I pathway of antigen presentation: the latter requires cytosolic delivery of antigen. In order to facilitate targeting of antigen to cytosol, the antigen was combined with the photosensitiser TPCS2a (disulfonated tetraphenyl chlorin) and administered intradermally to mice. The photosensitiser was activated by illumination of the injection site. This photochemical internalization (PCI) strongly increased the stimulation of CD8 T-cell responses as measured by antigen-specific proliferation and secretion of pro-inflammatory cytokines. Fluorescence microscopy showed that delivery to cytosol was TPCS2a dependent and occurred by light-induced disruption of TPCS2a- and antigen-containing endosomes. PCI-based vaccination prevented growth of malignant B16 cells as compared with vaccination without PCI. In conclusion, PCI represents a potent tool for delivery of antigens to cytosol for stimulation of cytotoxic CD8 T-cell responses. This study demonstrated a first proof-of-principle for PCI-mediated immunisation with potential application in cancer immunotherapy.
authors.affiliation: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland; Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; PCI Biotech AS, Strandveien 55, 1366 Lysaker, Norway.
authors.forename: Monika
authors.initials: M
authors.lastname: Håkerud
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 Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; PCI Biotech AS, Strandveien 55, 1366 Lysaker, Norway.
authors.forename: Pål Kristian
authors.initials: PK
authors.lastname: Selbo
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; D000941:Antigens / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics; D007114:Immunization; D007271:Injections, Intradermal; D008027:Light; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000528:radiation effects; D011166:Porphyrins / Q000494:pharmacology* / Q000528:radiation effects
chemical_list: D000941:Antigens; D004268:DNA-Binding Proteins; D017319:Photosensitizing Agents; D011166:Porphyrins; C499308:Rag2 protein, mouse; C559366:meso-tetraphenyl chlorin disulphonate; D010047:Ovalbumin
keywords: Antigen delivery; Cytosolic delivery; Cytotoxic T cells; Endosomes; Melanoma; Photochemical internalization