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dc.contributor.authorBrekke, Cecilie
dc.contributor.authorWang, Jian
dc.contributor.authorThuen, Marte
dc.contributor.authorGras Navarro, Andrea
dc.contributor.authorHuuse-Røneid, Else Marie
dc.contributor.authorThorsen, Frits Alan
dc.contributor.authorPoli, Aurélie
dc.contributor.authorZimmer, Jacques
dc.contributor.authorHaraldseth, Olav
dc.contributor.authorLie, Stein Atle
dc.contributor.authorEnger, Per Øyvind
dc.contributor.authorChekenya, Martha
dc.date.accessioned2015-03-03T15:07:50Z
dc.date.accessioned2015-08-12T13:45:53Z
dc.date.available2015-03-03T15:07:50Z
dc.date.available2015-08-12T13:45:53Z
dc.date.issued2014
dc.identifier.citationPLoS ONE 2014, 9(9)nb_NO
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11250/296433
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 761 and 1762 days posttreatment 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.nb_NO
dc.language.isoengnb_NO
dc.publisherPublic Library of Sciencenb_NO
dc.titleDynamic contrast enhanced MRI detects early response to adoptive NK cellular immunotherapy targeting the NG2 proteoglycan in a rat model of glioblastomanb_NO
dc.typeJournal articlenb_NO
dc.typePeer revieweden_GB
dc.date.updated2015-03-03T15:07:50Z
dc.source.volume9nb_NO
dc.source.journalPLoS ONEnb_NO
dc.source.issue9nb_NO
dc.identifier.doi10.1371/journal.pone.0108414
dc.identifier.cristin1187273
dc.description.localcode(c) 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.nb_NO


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