grant
Programming multi-pronged immune response to glioblastoma with IL-13Ra2/TGF-b CAR-T cell therapy.
Organization UNIVERSITY OF CALIFORNIA LOS ANGELESLocation LOS ANGELES, UNITED STATESPosted 1 Mar 2023Deadline 31 Jan 2028
NIHUS FederalResearch GrantFY2026Alpha Interleukin 2 ReceptorAntigensAntimorphic mutationAutopsyBSC-1 Cell Growth InhibitorBiopsyBone MarrowBone Marrow Reticuloendothelial SystemBone-Derived Transforming Growth FactorBrainBrain CancerBrain Nervous SystemC57BL/6 MouseCAR T cell therapyCAR T cellsCAR T therapyCAR modified T cellsCAR-TCAR-TsCIF-BCartilage-Inducing Factor-BCell BodyCell Communication and SignalingCell FunctionCell PhysiologyCell ProcessCell SignalingCell Surface AntigensCellsCellular FunctionCellular PhysiologyCellular ProcessCessation of lifeClinicClinical TreatmentCytometryDeathDominant NegativeDominant-Negative MutantDominant-Negative MutationEarly-Stage Clinical TrialsEncephalonEngineeringEnvironmentEpitope spreadingEvaluationFeedbackFlow CytofluorometriesFlow CytofluorometryFlow CytometryFlow MicrofluorimetryFlow MicrofluorometryGSC-1GIGenetic HeterogeneityGlial Cell TumorsGlial NeoplasmGlial TumorGlioblastomaGlioblastoma-Derived T-Cell Suppressor FactorGliomaGrade IV Astrocytic NeoplasmGrade IV Astrocytic TumorGrade IV AstrocytomaHeterogeneityHeterograftHeterologous TransplantationHumanIL-13RaIL-2RalphaIL-2RαIL13RA1IL13RA1 geneImmuneImmune mediated therapyImmune responseImmune systemImmunesImmunityImmunocompetentImmunofluorescenceImmunofluorescence ImmunologicImmunohistochemistryImmunohistochemistry Cell/TissueImmunohistochemistry Staining MethodImmunological Surface MarkersImmunologically Directed TherapyImmunomodulationImmunosuppressantsImmunosuppressionImmunosuppression EffectImmunosuppressive AgentsImmunosuppressive EffectImmunosuppressive drugImmunosuppressive treatmentImmunotherapyInfiltrationInflammatoryInterleukin-13 Receptor AlphaInterleukin-13 Receptor Alpha 1Intracellular Communication and SignalingIntravenousLibrariesLow Affinity Interleukin 2 ReceptorLymphatic cellLymphocyteLymphocyticMalignant Tumor of the BrainMalignant neoplasm of brainMedicalMesenchymalMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic TumorMiceMice MammalsMilk Growth FactorModelingModern ManMonitorMurineMusMyelogenousMyeloidMyeloid CellsMyeloid-derived suppressor cellsNR4Neoplasm MetastasisNeuroglial NeoplasmNeuroglial TumorNewly DiagnosedPatientsPhase 1 Clinical TrialsPhase I Clinical TrialsPhenotypePlatelet Transforming Growth FactorPlayPolyerginPreclinical dataPrimary Brain NeoplasmsPrimary Brain TumorsProliferatingReportingResectedRouteSafetySecondary NeoplasmSecondary TumorSignal TransductionSignal Transduction SystemsSignalingSpecificitySpleenSpleen Reticuloendothelial SystemStimulantSubcellular ProcessSurface AntigensSurvival RateT cells for CART-Cell Receptor BetaT-Cell Receptors beta-ChainT-CellsT-LymphocyteTGF BTGF-Beta 2TGF-Beta2TGF-b2TGF-betaTGF-beta ReceptorsTGF-βTGF-β ReceptorsTGF-β2TGFbetaTGFβTestingTimeToxic effectToxicitiesTransforming Growth Factor Beta 2Transforming Growth Factor betaTransforming Growth Factor beta ReceptorsTransforming Growth Factor β ReceptorsTransforming Growth Factor-Beta Family GeneTumor CellTumor PromotionTumor-Infiltrating LymphocytesTumor-associated macrophagesTumor-infiltrating immune cellsWorkXenograftXenograft ModelXenograft procedureXenotransplantationalpha-subunit, receptor, interleukin-2antigen spreadingbeta Chain Antigen T Cell Receptorbiological signal transductioncancer metastasiscancer microenvironmentcancer progressionchimeric antigen T cell receptorchimeric antigen receptorchimeric antigen receptor (CAR) T cell therapychimeric antigen receptor (CAR) T cellschimeric antigen receptor Tchimeric antigen receptor T cell therapychimeric antigen receptor T cellschimeric antigen receptor T therapychimeric antigen receptor fusion protein T-cellschimeric antigen receptor modified T cellsclinical interventionclinical therapyclinical translationclinical validationclinically translatablecytokineeffective therapyeffective treatmentengineered T cellsflow cytophotometrygenetically engineered T-cellsglial-derived tumorglioblastoma multiformehost responseimmune cell infiltration of tumorsimmune cells infiltrating the tumorimmune cells that infiltrate the tumorimmune competentimmune modulationimmune regulationimmune suppressionimmune suppressive activityimmune suppressive agentimmune suppressive functionimmune suppressorimmune system responseimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmuno therapyimmunogenimmunologic reactivity controlimmunomodulatoryimmunoregulationimmunoregulatoryimmunoresponseimmunosuppressive activityimmunosuppressive functionimmunosuppressive myeloid cellsimmunosuppressive responseimmunosuppressive substanceimmunosuppressorimprovedin vivoinfiltration of tumors by immune cellsinterleukin-2Ralphaintratumoral immune cellintratumoral immune infiltratelymph cellmouse modelmurine modelmyeloid suppressor cellsmyeloid-derived suppressive cellsnecropsyneoplasm progressionneoplastic cellneoplastic progressionneuroglia neoplasmneuroglia tumornovelphase I protocolpostmortempreclinical findingspreclinical informationpreservationpressurerecruitresponsescRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingspongioblastoma multiformesuppressive myeloid cellstargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmentthymus derived lymphocytetransforming growth factor beta2transforming growth factor β2transgenic T- cellstranslational opportunitiestranslational potentialtreatment grouptrial regimentrial treatmenttumortumor cell metastasistumor growthtumor immune celltumor immune infiltratetumor infiltration of immune cellstumor microenvironmenttumor progressionxeno-transplantxeno-transplantationxenograft transplant modelxenotransplant model
Description preview
ABSTRACT
Glioblastoma multiforme (GBM) is the most common type of primary brain tumor, with a five-year survival rate
of only 5.5%. Chimeric antigen receptor (CAR)-T cell therapy has shown safety but limited efficacy in the
treatment of patients with GBM to date. GBM is characterized by dramatic antigen heterogeneity, thus
immunotherapy targeting…
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