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dc.contributor.authorKhairuddin, Norliana
dc.contributor.authorBlake, Stephen J
dc.contributor.authorFirdaus, Farah
dc.contributor.authorSteptoe, Raymond J
dc.contributor.authorBehlke, Mark A
dc.contributor.authorHertzog, Paul J
dc.contributor.authorMcMillan, Nigel AJ
dc.date.accessioned2018-11-16T01:48:50Z
dc.date.available2018-11-16T01:48:50Z
dc.date.issued2014
dc.identifier.issn0818-9641
dc.identifier.doi10.1038/icb.2013.75
dc.identifier.urihttp://hdl.handle.net/10072/138134
dc.description.abstractSmall interfering RNAs (siRNAs) to inhibit oncogene expression and also to activate innate immune responses via Toll-like receptor (TLR) recognition have been shown to be beneficial as anti-cancer therapy in certain cancer models. In this study, we investigated the effects of local versus systemic delivery of such immune-stimulating Dicer-substrate siRNAs (IS-DsiRNAs) on a human papillomavirus (HPV)-driven tumour model. Localized siRNA delivery using intratumour injection of siRNA was able to increase siRNA delivery to the tumour compared with intravenous (IV) delivery and potently activated innate immune responses. However, IV injection remained the more effective delivery route for reducing tumour growth. Although IS-DsiRNAs activated innate immune cells and required interferon-a (IFNa) for full effect on tumour growth, we found that potent silencing siRNA acting independently of IFNa were overall more effective at inhibiting TC-1 tumour growth. Other published work utilising IS-siRNAs have been carried out on tumour models with low levels of major histocompatibility complex (MHC)-class 1, a target of natural killer cells that are potently activated by IS-siRNA. As TC-1 cells used in our study express high levels of MHC-class I, the addition of the immunostimulatory motifs may not be as beneficial in this particular tumour model. Our data suggest that selection of siRNA profile and delivery method based on tumour environment is crucial to developing siRNA-based therapies.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherNature Publishing Group
dc.publisher.placeUnited Kingdom
dc.relation.ispartofpagefrom156
dc.relation.ispartofpageto163
dc.relation.ispartofissue2
dc.relation.ispartofjournalImmunology and Cell Biology
dc.relation.ispartofvolume92
dc.subject.fieldofresearchCancer Therapy (excl. Chemotherapy and Radiation Therapy)
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchcode111204
dc.subject.fieldofresearchcode1107
dc.subject.fieldofresearchcode0601
dc.titleIn vivo comparison of local versus systemic delivery of immunostimulating siRNA in HPV-driven tumours
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionPost-print
gro.rights.copyright© 2013 Nature Publishing Group. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
gro.hasfulltextFull Text
gro.griffith.authorMcMillan, Nigel


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