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dc.contributor.authorHaug, Markus
dc.contributor.authorBrede, Gaute
dc.contributor.authorHåkerud, Monika
dc.contributor.authorNedberg, Anne Grete
dc.contributor.authorGederaas, Odrun Arna
dc.contributor.authorFlo, Trude Helen
dc.contributor.authorEdwards, Victoria Tudor
dc.contributor.authorSelbo, Pål Kristian
dc.contributor.authorHøgset, Anders
dc.contributor.authorHalaas, Øyvind
dc.date.accessioned2018-04-10T12:12:03Z
dc.date.available2018-04-10T12:12:03Z
dc.date.created2018-04-09T08:47:57Z
dc.date.issued2018
dc.identifier.issn1664-3224
dc.identifier.urihttp://hdl.handle.net/11250/2493453
dc.description.abstractEffective 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 30-100-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.nb_NO
dc.language.isoengnb_NO
dc.publisherFrontiers Medianb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titlePhotochemical internalization of peptide antigens provides a novel strategy to realize therapeutic cancer vaccinationnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.volume9nb_NO
dc.source.journalFrontiers in Immunologynb_NO
dc.identifier.doi10.3389/fimmu.2018.00650
dc.identifier.cristin1578226
dc.relation.projectNorges forskningsråd: 223255nb_NO
dc.relation.projectSamarbeidsorganet mellom Helse Midt-Norge og NTNU: 46056834nb_NO
dc.relation.projectNorges forskningsråd: 235365nb_NO
dc.description.localcode© 2018 Haug, Brede, Håkerud, Nedberg, Gederaas, Flo, Edwards, Selbo, Høgset and Halaas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).nb_NO
cristin.unitcode194,65,15,0
cristin.unitcode194,66,25,0
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.unitnameInstitutt for kjemi
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.fulltextpreprint
cristin.fulltextpostprint
cristin.qualitycode1


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