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dc.contributor.authorPowell, Katie L
dc.contributor.authorStephens, Alexandre S
dc.contributor.authorRalph, Stephen J
dc.date.accessioned2018-07-16T06:09:56Z
dc.date.available2018-07-16T06:09:56Z
dc.date.issued2015
dc.identifier.issn0340-7004
dc.identifier.doi10.1007/s00262-015-1695-3
dc.identifier.urihttp://hdl.handle.net/10072/101089
dc.description.abstractAt present, there are no vaccines approved for the prevention or treatment of malignant melanoma, despite the amount of time and resources that has been invested. In this study, we aimed to develop a self-contained vaccine capable of directly stimulating anticancer CD8+ T-cell immune responses. To achieve this, three whole-cell melanoma vaccines were developed expressing 4-1BBL or B7.1 T-cell co-stimulatory molecules individually or in combination. The ability of engineered vaccine cell lines to stimulate potent anticancer immune responses in C57BL/6 mice was assessed. Mice vaccinated with cells overexpressing both 4-1BBL and B7.1 (B16-F10-4-1BBL-B7.1-IFNγ/β anticancer vaccine) displayed the greatest increases in CD8+ T-cell populations (1.9-fold increase versus control within spleens), which were efficiently activated following antigenic stimulation, resulting in a 10.7-fold increase in cancer cell cytotoxicity relative to control. The enhanced immune responses in B16-F10-4-1BBL-B7.1-IFNγ/β-vaccinated mice translated into highly efficient rejection of live tumour burdens and conferred long-term protection against repeated tumour challenges, which were likely due to enhanced effector memory T-cell populations. Similar results were observed when dendritic cell (DC)-deficient LTα−/− mice were treated with the B16-F10-4-1BBL-B7.1-IFNγ/β anticancer vaccine, suggesting that the vaccine can directly stimulate CD8+ T-cell responses in the context of severely reduced DCs. This study shows that the B16-F10-4-1BBL-B7.1-IFNγ/β anticancer vaccine acted as a highly effective antigen-presenting cell and is likely to be able to directly stimulate CD8+ T-cells, without requiring co-stimulatory signals from either CD4+ T-cells or DCs, and warrants translation of this technology into the clinical setting.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofpagefrom861
dc.relation.ispartofpageto872
dc.relation.ispartofissue7
dc.relation.ispartofjournalCancer Immunology, Immunotherapy
dc.relation.ispartofvolume64
dc.subject.fieldofresearchImmunology not elsewhere classified
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchcode110799
dc.subject.fieldofresearchcode1107
dc.titleDevelopment of a potent melanoma vaccine capable of stimulating CD8+ T-cells independently of dendritic cells in a mouse model
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Medical Science
gro.hasfulltextNo Full Text
gro.griffith.authorStephens, Alexandre
gro.griffith.authorRalph, Stephen J.
gro.griffith.authorPowell, Katie


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