Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/9988
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dc.contributor.authorPerera, Rushika Men
dc.contributor.authorNarita, Yoshitakaen
dc.contributor.authorFurnari, Frank Ben
dc.contributor.authorGan, Hui Ken
dc.contributor.authorMurone, Carmelen
dc.contributor.authorAhlkvist, Marikaen
dc.contributor.authorLuwor, Rodney Ben
dc.contributor.authorBurgess, Antony Wen
dc.contributor.authorStockert, Elisabethen
dc.contributor.authorJungbluth, Achim Aen
dc.contributor.authorOld, Lloyd Jen
dc.contributor.authorCavenee, Webster Ken
dc.contributor.authorScott, Andrew Men
dc.contributor.authorJohns, Terrance Gen
dc.date.accessioned2015-05-15T23:17:38Z
dc.date.available2015-05-15T23:17:38Z
dc.date.issued2005-09-01en
dc.identifier.citationClinical Cancer Research; 11(17): 6390-9en
dc.identifier.govdoc16144944en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/9988en
dc.description.abstractMonoclonal antibody (mAb) 806 is a novel epidermal growth factor receptor (EGFR) antibody with significant antitumor activity that recognizes a mutant EGFR commonly expressed in glioma known as delta2-7 EGFR (de2-7 EGFR or EGFRvIII) and a subset of the wild-type (wt) EGFR found in cells that overexpress the receptor. We have used two human xenograft mouse models to examine the efficacy of mAb 806 in combination with mAb 528, a prototypical anti-EGFR antibody with similar specificity to cetuximab. Treatment of nude mice, bearing s.c. or i.c. tumor human xenografts expressing the wt or de2-7 EGFR, with mAbs 806 and 528 in combination resulted in additive and in some cases synergistic, antitumor activity. Interestingly, mAb 528 was also effective against xenografts expressing the ligand independent de2-7 EGFR when used as a single agent, showing that its antitumor activity is not merely mediated through inhibition of ligand binding. When used as single agents, neither mAbs 806 or 528 induced down-regulation of the de2-7 EGFR either in vitro or in vivo. In contrast, the combination of antibodies produced a rapid and dramatic decrease in the total cell surface de2-7 EGFR both in vitro and in xenografts. Consistent with this decrease in total cell surface de2-7 EGFR, we observed up-regulation of the cell cycle inhibitor p27(KIP1) and a decrease in tumor cell proliferation as measured by Ki-67 immunostaining when the antibodies were used in combination in vivo. Thus, mAb 806 can synergize with other EGFR-specific antibodies thereby providing a rationale for its translation into the clinic.en
dc.language.isoenen
dc.subject.otherAnimalsen
dc.subject.otherAntibodies, Monoclonal.metabolism.pharmacologyen
dc.subject.otherAntineoplastic Agents.pharmacologyen
dc.subject.otherCell Cycle Proteins.metabolismen
dc.subject.otherCell Proliferationen
dc.subject.otherCyclin-Dependent Kinase Inhibitor p27en
dc.subject.otherDrug Synergismen
dc.subject.otherDrug Therapy, Combinationen
dc.subject.otherFemaleen
dc.subject.otherGene Expression Regulation, Neoplasticen
dc.subject.otherGlioma.drug therapy.genetics.pathologyen
dc.subject.otherHumansen
dc.subject.otherKi-67 Antigen.metabolismen
dc.subject.otherMiceen
dc.subject.otherMice, Nudeen
dc.subject.otherMutationen
dc.subject.otherReceptor, Epidermal Growth Factor.genetics.immunologyen
dc.subject.otherSurvival Rateen
dc.subject.otherTumor Cells, Cultureden
dc.subject.otherTumor Suppressor Proteins.metabolismen
dc.subject.otherXenograft Model Antitumor Assaysen
dc.titleTreatment of human tumor xenografts with monoclonal antibody 806 in combination with a prototypical epidermal growth factor receptor-specific antibody generates enhanced antitumor activity.en
dc.typeJournal Articleen
dc.identifier.journaltitleClinical Cancer Researchen
dc.identifier.affiliationLudwig Institute for Cancer Research, Melbourne Branch, Tumor Targeting Program, Austin Hospital, Heidelberg, Victoria, Australiaen
dc.identifier.doi10.1158/1078-0432.CCR-04-2653en
dc.description.pages6390-9en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/16144944en
dc.type.austinJournal Articleen
local.name.researcherGan, Hui K
item.languageiso639-1en-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.openairetypeJournal Article-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
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