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dc.contributor.authorBrekke, Cecilieen_US
dc.contributor.authorWang, Jianen_US
dc.contributor.authorThuen, Marteen_US
dc.contributor.authorGras Navarro, Andreaen_US
dc.contributor.authorHuuse-Røneid, Else Marieen_US
dc.contributor.authorThorsen, Frits Alanen_US
dc.contributor.authorPoli, Aurélieen_US
dc.contributor.authorZimmer, Jacquesen_US
dc.contributor.authorHaraldseth, Olaven_US
dc.contributor.authorLie, Stein Atleen_US
dc.contributor.authorEnger, Per Øyvinden_US
dc.contributor.authorChekenya, Marthaen_US
dc.date.accessioned2015-03-18T13:33:01Z
dc.date.available2015-03-18T13:33:01Z
dc.date.issued2014-09-30eng
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/1956/9583
dc.description.abstractThere are currently no established radiological parameters that predict response to immunotherapy. We hypothesised that multiparametric, longitudinal magnetic resonance imaging (MRI) of physiological parameters and pharmacokinetic models might detect early biological responses to immunotherapy for glioblastoma targeting NG2/CSPG4 with mAb9.2.27 combined with natural killer (NK) cells. Contrast enhanced conventional T1-weighted MRI at 7±1 and 17±2 days post-treatment failed to detect differences in tumour size between the treatment groups, whereas, follow-up scans at 3 months demonstrated diminished signal intensity and tumour volume in the surviving NK+mAb9.2.27 treated animals. Notably, interstitial volume fraction (ve), was significantly increased in the NK+mAb9.2.27 combination therapy group compared mAb9.2.27 and NK cell monotherapy groups (p = 0.002 and p = 0.017 respectively) in cohort 1 animals treated with 1 million NK cells. ve was reproducibly increased in the combination NK+mAb9.2.27 compared to NK cell monotherapy in cohort 2 treated with increased dose of 2 million NK cells (p<0.0001), indicating greater cell death induced by NK+mAb9.2.27 treatment. The interstitial volume fraction in the NK monotherapy group was significantly reduced compared to mAb9.2.27 monotherapy (p<0.0001) and untreated controls (p = 0.014) in the cohort 2 animals. NK cells in monotherapy were unable to kill the U87MG cells that highly expressed class I human leucocyte antigens, and diminished stress ligands for activating receptors. A significant association between apparent diffusion coefficient (ADC) of water and ve in combination NK+mAb9.2.27 and NK monotherapy treated tumours was evident, where increased ADC corresponded to reduced ve in both cases. Collectively, these data support histological measures at end-stage demonstrating diminished tumour cell proliferation and pronounced apoptosis in the NK+mAb9.2.27 treated tumours compared to the other groups. In conclusion, ve was the most reliable radiological parameter for detecting response to intralesional NK cellular therapy.en_US
dc.language.isoengeng
dc.publisherPublic Library of Scienceeng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/eng
dc.titleDynamic contrast enhanced MRI detects early response to adoptive NK cellular immunotherapy targeting the NG2 proteoglycan in a rat model of glioblastomaen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2015-03-03T15:07:57Zen_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2014 Rygh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.source.articlenumbere108414
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0108414
dc.identifier.cristin1187273
dc.source.journalPLoS ONE
dc.source.409
dc.source.149


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