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dc.contributor.authorDebinski, Waldemaren_US
dc.contributor.authorDickinson, Peteren_US
dc.contributor.authorRossmeisl, John H.en_US
dc.contributor.authorRobertson, Johnen_US
dc.contributor.authorGibo, Denise M.en_US
dc.date.accessioned2018-10-16T16:41:24Z
dc.date.available2018-10-16T16:41:24Z
dc.date.issued2013-10-16en_US
dc.identifier.othere77719en_US
dc.identifier.urihttp://hdl.handle.net/10919/85384
dc.description.abstractInterleukin 13 receptor alpha 2 (IL-13RA2) is over-expressed in a vast majority of human patients with high-grade astrocytomas like glioblastoma. Spontaneous astrocytomas in dogs resemble human disease and have been proposed as translational model system for investigation of novel therapeutic strategies for brain tumors. We have generated reagents for both detection and therapeutic targeting of IL-13RA2 in human and canine brain tumors. Peptides from three different regions of IL-13RA2 with 100% sequence identity between human and canine receptors were used as immunogens for generation of monoclonal antibodies. Recombinant canine mutant IL-13 (canIL-13.E13K) and canIL-13.E13K based cytotoxin were also produced. The antibodies were examined for their immunoreactivities in western blots, immunohistochemistry, immunofluorescence and cell binding assays using human and canine tumor specimen sections, tissue lysates and established cell lines; the cytotoxin was tested for specific cell killing. Several isolated MAbs were immunoreactive to IL-13RA2 in western blots of cell and tissue lysates from glioblastomas from both human and canine patients. Human and canine astrocytomas and oligodendrogliomas were also positive for IL-13RA2 to various degrees. Interestingly, both human and canine meningiomas also exhibited strong reactivity. Normal human and canine brain samples were virtually negative for IL-13RA2 using the newly generated MAbs. MAb 1E10B9 uniquely worked on tissue specimens and western blots, bound live cells and was internalized in GBM cells over-expressing IL-13RA2. The canIL-13.E13K cytotoxin was very potent and specific in killing canine GBM cell lines. Thus, we have obtained several monoclonal antibodies against IL-13RA2 cross-reacting with human and canine receptors. In addition to GBM, other brain tumors, such as high grade oligodendrogliomas, meningiomas and canine choroid plexus papillomas, appear to express the receptor at high levels and thus may be appropriate candidates for IL-13RA2-targeted imaging/therapies. Canine spontaneous primary brain tumors represent an excellent translational model for human counterparts.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.publisherPLOSen_US
dc.rightsCreative Commons Attribution 4.0en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleNew Agents for Targeting of IL-13RA2 Expressed in Primary Human and Canine Brain Tumorsen_US
dc.typeArticle - Refereeden_US
dc.description.versionPeer Revieweden_US
dc.title.serialPLOS ONEen_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0077719en_US
dc.identifier.volume8en_US
dc.identifier.issue10en_US
dc.type.dcmitypeTexten_US
dc.identifier.pmid24147065en_US
dc.identifier.eissn1932-6203en_US


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Creative Commons Attribution 4.0
License: Creative Commons Attribution 4.0