grant
Project 3: Hedgehog Inhibition to Enhance Response to ICI Therapy
Organization UNIVERSITY OF PITTSBURGH AT PITTSBURGHLocation PITTSBURGH, UNITED STATESPosted 1 Sept 2023Deadline 31 Aug 2028
NIHUS FederalResearch GrantFY2025BIGH3BindingBiopsyBloodBlood PlasmaBlood Reticuloendothelial SystemBlood monocyteBody TissuesBone-Derived Transforming Growth FactorCD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCDB1CDGG1CSD1CSD2CSD3CXCL9CXCL9 geneCancer PatientCarcinomaCell BodyCell LocomotionCell MigrationCell MovementCellsCellular MigrationCellular MotilityCheckpoint inhibitorChemotactic CytokinesClinical TrialsCorrelative StudyCytotoxic cellDataDoseEffector CellEpithelial cancerErinaceidaeEventExclusionFibroblastsFosteringHedgehog (Hh) signal transduction pathwayHedgehogsHomologous Chemotactic CytokinesHumanHumigImmuneImmune RegulatorsImmune checkpoint inhibitorImmune infiltratesImmunesImmunomodulatorsImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapeutic agentIn VitroInfiltrationIntercrinesK lymphocyteLCD1LeadLinkMIG GeneMacrophageMalignant CellMalignant Epithelial NeoplasmsMalignant Epithelial TumorsMalignant Ovarian NeoplasmMalignant Ovarian TumorMalignant Tumor of the OvaryMalignant neoplasm of ovaryMarrow monocyteMeasuresMediatingMediatorMesenchymal Progenitor CellMesenchymal Stem CellsMesenchymal progenitorMesenchymal stromal/stem cellsMiceMice MammalsMilk Growth FactorModelingModern ManMolecular InteractionMurineMusMyeloid CellsMφNK CellsNatural Killer CellsOvarian CarcinomaOvary CancerOvary CarcinomaPBMCPD-L1 antibodyPatient outcomePatient-Centered OutcomesPatient-Focused OutcomesPatientsPb elementPeripheralPeripheral Blood Mononuclear CellPhasePhase 2 Clinical TrialsPhase II Clinical TrialsPhenotypePhysiologic pulsePlasmaPlasma SerumPlatelet Transforming Growth FactorPlatinumPlatinum BlackPrediction of Response to TherapyProgression-Free SurvivalsProteinsPt elementPulseRecurrenceRecurrentReportingResistanceReticuloendothelial System, Serum, PlasmaRoleSCYB9SIS cytokinesSafetyT cell receptor repertoire sequencingT cell receptor sequencingT cell regulationT-Cell ActivationT-CellsT-LymphocyteT8 CellsT8 LymphocytesTCR repertoire sequencingTCR sequencingTCR-seqTCRseqTGF BTGF-betaTGF-βTGFBITGFBI geneTGFbetaTGFβTestingTissuesTransforming Growth Factor betaTransforming Growth Factor-Beta Family GeneTumor ImmunityTumor TissueTumor-associated macrophagesTumor-infiltrating immune cellsaPD-L1aPD-L1 antibodiesactivate T cellsanti programmed cell death ligand 1anti programmed cell death protein ligand 1anti-PD-(L)1anti-PD-L1anti-PD-L1 antibodiesanti-PD-L1 monoclonal antibodiesanti-PDL-1anti-PDL1anti-PDL1 antibodiesanti-tumor immunityantiPD-L1antitumor immunityarmcancer cellcancer immunitycancer microenvironmentcell motilitycheck point immunotherapycheck point inhibitor therapycheck point inhibitory therapycheck point therapycheckpoint immunotherapycheckpoint inhibitor therapycheckpoint inhibitory therapycheckpoint therapychemoattractant cytokinechemokinecrg-10cytokinedesigndesigningepithelial carcinomagenetic approachgenetic strategyheavy metal Pbheavy metal leadhedgehog signalinghedgehog signaling pathwayhh signaling pathwayhumanized micehumanized mouseimmune cell infiltrateimmune cell infiltration of tumorsimmune cells infiltrating the tumorimmune cells that infiltrate the tumorimmune check point inhibitorimmune check point therapyimmune checkpoint therapyimmune drugsimmune microenvironmentimmune modulatorsimmune suppressionimmune suppressive activityimmune suppressive functionimmune-based therapeuticsimmunologic therapeuticsimmunomodulatory moleculesimmunoregulatorimmunoregulatory moleculesimmunosuppressive activityimmunosuppressive functionimmunosuppressive microenvironmentimmunosuppressive responseimmunosuppressive tumor microenvironmentimmunotherapeuticsimmunotherapy agentimproved outcomein vivoinfiltration of tumors by immune cellsinhibitorinhibitor druginhibitor therapeuticinhibitor therapyintratumoral immune cellintratumoral immune infiltrateisletmesenchymal stromal cellmesenchymal stromal progenitor cellsmesenchymal-derived stem cellsmigrationmonocytemouse modelmurine modelnanostringneutralizing antibodynew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetovarian cancerpatient oriented outcomespatient prognosispatient responsepatient specific responsephase II protocolpre-clinical studypreclinical studypredict responsivenesspredict therapeutic responsepredict therapy responsepredicting responsepredictive biological markerpredictive biomarkerspredictive markerpredictive molecular biomarkerprimary end pointprimary endpointrecruitresistantresponseresponse to therapyresponse to treatmentresponsive patientrestorationscRNA sequencingscRNA-seqsecondary end pointsecondary endpointsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsmoothened signaling pathwaysocial roletherapeutic outcometherapeutic responsetherapeutic targettherapy outcometherapy predictiontherapy responsethymus derived lymphocytetranslational studytreatment predictiontreatment responsetreatment response predictiontreatment responsivenesstumortumor immune celltumor immune infiltratetumor immune microenvironmenttumor infiltration of immune cellstumor microenvironmenttumor-immune system interactionsαPD-L1αPD-L1 antibodiesαPDL1
Description preview
SUMMARY/ABSTRACT – PROJECT 3
When effective, immune checkpoint inhibitor (ICI) therapy can significantly improve the outcome of patients with
ovarian cancer (OvCa). However, only 10-20% of OvCa patients respond to ICI therapy. One reason for the low
ICI response rate of OvCa may be OvCa’s unique immunosuppressive tumor microenvironment (TME),…
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