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dc.contributor.authorMcCormack, Emmeten_US
dc.contributor.authorAdams, Katherine J.en_US
dc.contributor.authorHassan, Namir J.en_US
dc.contributor.authorKotian, Akhilen_US
dc.contributor.authorLissin, Nikolai M.en_US
dc.contributor.authorSami, Malkiten_US
dc.contributor.authorMujic, Majaen_US
dc.contributor.authorOsdal, Terezaen_US
dc.contributor.authorGjertsen, Bjørn Toreen_US
dc.contributor.authorBaker, Deborahen_US
dc.contributor.authorPowlesland, Alex S.en_US
dc.contributor.authorAleksic, Milosen_US
dc.contributor.authorVuidepot, Anneliseen_US
dc.contributor.authorMorteau, Olivieren_US
dc.contributor.authorSutton, Deborah H.en_US
dc.contributor.authorJune, Carl H.en_US
dc.contributor.authorKalos, Michaelen_US
dc.contributor.authorAshfield, Rebeccaen_US
dc.contributor.authorJakobsen, Bent K.en_US
dc.date.accessioned2013-03-07T13:49:57Z
dc.date.available2013-03-07T13:49:57Z
dc.date.issued2012-12eng
dc.identifier.issn1432-0851
dc.identifier.issn0340-7004
dc.identifier.urihttps://hdl.handle.net/1956/6397
dc.descriptionElectronic supplementary material The online version of this article (doi:10.1007/s00262-012-1384-4) contains supplementary material, which is available to authorized users.eng
dc.description.abstractNY-ESO-1 and LAGE-1 are cancer testis antigens with an ideal profile for tumor immunotherapy, combining up-regulation in many cancer types with highly restricted expression in normal tissues and sharing a common HLA-A*0201 epitope, 157–165. Here, we present data to describe the specificity and anti-tumor activity of a bifunctional ImmTAC, comprising a soluble, high-affinity T-cell receptor (TCR) specific for NY-ESO-1157–165 fused to an anti-CD3 scFv. This reagent, ImmTAC-NYE, is shown to kill HLA-A2, antigen-positive tumor cell lines, and freshly isolated HLA-A2- and LAGE-1-positive NSCLC cells. Employing time-domain optical imaging, we demonstrate in vivo targeting of fluorescently labelled high-affinity NYESO-specific TCRs to HLA-A2-, NYESO- 1157–165-positive tumors in xenografted mice. In vivo ImmTAC-NYE efficacy was tested in a tumor model in which human lymphocytes were stably co-engrafted into NSG mice harboring tumor xenografts; efficacy was observed in both tumor prevention and established tumor models using a GFP fluorescence readout. Quantitative RT-PCRwas used to analyze the expression of both NY-ESO-1 and LAGE-1 antigens in 15 normal tissues, 5 cancer cell lines, 10 NSCLC, and 10 ovarian cancer samples. Overall, LAGE-1 RNA was expressed at a greater frequency and at higher levels than NY-ESO-1 in the tumor samples. These data support the clinical utility of ImmTAC-NYE as an immunotherapeutic agent for a variety of cancers.en_US
dc.language.isoengeng
dc.publisherSpringer Verlageng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/eng
dc.subjectBi-specific TCReng
dc.subjectImmTACeng
dc.subjectCancer immunotherapyeng
dc.subjectNY-ESO-1eng
dc.subjectLAGE-1eng
dc.subjectTime-domaineng
dc.titleBi-specific TCR-anti CD3 redirected T-cell targeting of NY-ESO-1- and LAGE-1-positive tumorsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.description.versionpublishedVersionen_US
dc.rights.holderThe Author(s) 2012. This article is published with open access at Springerlink.com
dc.identifier.doihttps://doi.org/10.1007/s00262-012-1384-4
dc.identifier.cristin1034708
dc.source.journalCancer Immunology, Immunotherapy


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