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Synergistic microglial activation and tumor cell killing for improved GBM response
NIHUS FederalResearch GrantFY202521+ years oldAblationAbscopal effectAdultAdult HumanAffinityAffinotoxinsAnimal ModelAnimal Models and Related StudiesAnimalsAntibody FragmentsAntigen PresentationAntigen-Presenting CellsAntigensAntitumor ResponseAutomobile DrivingBindingBp50BrainBrain CancerBrain NeoplasiaBrain NeoplasmsBrain Nervous SystemBrain TumorsCD11cCD40CD8CD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCD8BCD8B1CD8B1 geneCDW40Cancer GenesCancer-Promoting GeneCell BodyCellsCellular ExpansionCellular GrowthClinicClinicalClosure by LigationCombined Modality TherapyContralateralCytotoxic ChemotherapyCytotoxic TherapyCytotoxin-Antibody ConjugatesDeath RateDedicationsDevelopmentDiseaseDisorderDisseminated SclerosisEGF ReceptorEGFRERBB ProteinEarly-Stage Clinical TrialsEducationEducational aspectsEffectivenessEncephalonEpidermal Growth Factor ReceptorEpidermal Growth Factor Receptor KinaseEpidermal Growth Factor Receptor Protein-Tyrosine KinaseEpidermal Growth Factor-Urogastrone ReceptorsGeneral RadiologyGenerationsGlial Cell TumorsGlial NeoplasmGlial TumorGlioblastomaGliomaGoalsGrade IV Astrocytic NeoplasmGrade IV Astrocytic TumorGrade IV AstrocytomaHER1Hortega cellITGAXITGAX geneImmuneImmunesImmunocompetentImmunoglobulin FragmentsImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotoxin TherapyImmunotoxinsIn VitroIndividualInflammatoryInfusionInfusion proceduresIpsilateralLYT3LigationMGC9013MacrophageMalignant Tumor of the BrainMalignant neoplasm of brainMediatingMediatorMiceMice MammalsMicrogliaModelingMolecularMolecular InteractionMonoclonal Antibody-Toxin ConjugatesMultimodal TherapyMultimodal TreatmentMultiple SclerosisMurineMusMφNeuroglial NeoplasmNeuroglial TumorOncogenesOutcomePatientsPhagocytosisPhase 1 Clinical TrialsPhase I Clinical TrialsPhenotypePrimary Brain NeoplasmsPrimary Brain TumorsProductivityRadiographyRadiologyRadiology SpecialtyRecombinant AntibodyRecurrenceRecurrentResearchRoentgenographyRoleT cell infiltrationT cell responseT-Cell ActivationT-CellsT-LymphocyteT8 CellsT8 LymphocytesTGF-alpha ReceptorTNFRSF5TNFRSF5 geneTeff cellTestingTherapeuticToxin-Antibody ConjugatesToxin-Antibody HybridsTransforming GenesTransforming Growth Factor alpha ReceptorTranslatingTumor AntigensTumor CellTumor ImmunityTumor Necrosis Factor Receptor Superfamily Member 5 GeneTumor PromotionTumor-Associated AntigenTumor-associated macrophagesUrogastrone ReceptorVariantVariationabscopal activityabscopal responseaccessory cellactivate T cellsadulthoodanti-tumor immune responseanti-tumor immunityanti-tumor responseantitumor immunityc-erbB-1c-erbB-1 Proteincancer antigenscancer immunitycancer microenvironmentcell growthcell killingclinical translationclinically translatablecombination therapycombined modality treatmentcombined treatmentcytotoxiccytotoxic CD8 T cellscytotoxic CD8 T lymphocytedefined contributiondevelopmentaldrivingeffective therapyeffective treatmenteffector T cellerbB-1erbB-1 Proto-Oncogene ProteinerbBlgitter cellglial activationglial cell activationglial-derived tumorglioblastoma multiformeimmune competentimmune microenvironmentimmune suppressionimmune suppressive activityimmune suppressive functionimmune suppressive macrophagesimmunogenimmunosuppressive activityimmunosuppressive functionimmunosuppressive macrophagesimmunosuppressive microenvironmentimmunosuppressive responseimmunosuppressive tumor microenvironmentimprovedin vivoinfusionsinnovateinnovationinnovativeinsightinsular sclerosismesogliamicroglial cellmicrogliocytemodel of animalmortality ratemortality ratiomulti-modal therapymulti-modal treatmentmutantneoplastic cellneuroglia neoplasmneuroglia tumornew approachesnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapeuticsnew therapynew therapy approachesnew treatment approachnew treatment strategynext generation therapeuticsnovelnovel approachesnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel strategiesnovel strategynovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapeuticsnovel therapynovel therapy approachp50patient responsepatient specific responsepatient subclasspatient subclusterpatient subgroupspatient subpopulationspatient subsetspatient subtypesperivascular glial cellphase I protocolpre-clinicalpre-clinical studypreclinicalpreclinical studyproto-oncogene protein c-erbB-1public health relevanceradiological imagingresponseresponsive patientsocial rolespongioblastoma multiformesubcutaneoussubdermalsurvival outcomethymus derived lymphocytetranscriptome profilingtranscriptomic profilingtranscriptomicstumortumor immune microenvironmenttumor microenvironmenttumor-immune system interactionstumor-specific antigentumorigenictumors in the brain
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PROJECT SUMMARY/ABSTRACT
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Current therapies remain
unsuccessful in improving overall survival; thus, the identification of novel therapies for GBM is critical. We have
pioneered a novel, targeted immunotoxin (IT)-based cytotoxic therapy, D2C7-IT, that targets…
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