grant
Tumor microenvironment-dependent therapy resistance
Organization CHILDREN'S HOSP OF PHILADELPHIALocation PHILADELPHIA, UNITED STATESPosted 18 Sept 2017Deadline 28 Feb 2029
NIHUS FederalResearch GrantFY20263-D3-Dimensional3DActivated Natural Killer CellAdrenergic AgentsAdrenergic DrugsAdrenergicsAssayAttentionB cell differentiation factorB cell stimulating factor 2B-Cell Differentiation FactorB-Cell Differentiation Factor-2B-Cell Stimulatory Factor-2B7-H3B7H3BCDFBSF-2BSF2BioassayBiological AssayBone-Derived Transforming Growth FactorCAR T cellsCAR modified T cellsCAR-TCAR-TsCCL2CCL2 geneCD276CD276 geneCancersCell BodyCell LocomotionCell MigrationCell MovementCell TherapyCell-Extracellular MatrixCellsCellular MigrationCellular MotilityChemokine, CC Motif, Ligand 2Chemotactic CytokinesComplexCytometryCytotoxic ChemotherapyCytotoxic TherapyCytotoxic cellDataDepositDepositionDevelopmentDominant Negative ReceptorDrug resistanceECMEngineeringEnvironmentEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessExtracellular MatrixFibroblastsFundingGeneralized GrowthGeneticGrowthHPGFHepatocyte-Stimulating FactorHeterogeneityHeterograftHeterologous TransplantationHomologous Chemotactic CytokinesHumanHybridoma Growth FactorIFN-beta 2IFNB2IL-6IL6 ProteinImageImmuneImmune infiltratesImmune mediated therapyImmunesImmuno-ChemotherapyImmunochemotherapyImmunodeficient MouseImmunofluorescenceImmunofluorescence ImmunologicImmunoglobulin Enhancer-Binding ProteinImmunologically Directed TherapyImmunotherapyIn VitroIndividualInfiltrationInflammatoryIntercrinesInterleukin-6InvadedJAK-2JAK2JAK2 geneJAK2 proteinJV18JV18-1Janus kinase 2K lymphocyteKnowledgeLeadLytotoxicityMADH2MADH2 geneMADR2MCAFMCP-1MCP1MGI-2Malignant NeoplasmsMalignant TumorMediatingMesenchymalMesenchymal Progenitor CellMesenchymal Stem CellsMesenchymal progenitorMesenchymal stromal/stem cellsMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic TumorMilk Growth FactorModelingModern ManMonocyte Chemoattractant Protein-1Monocyte Chemotactic Protein-1Monocyte Chemotactic and Activating FactorMonocyte Chemotactic and Activating ProteinMonocyte Chemotactive and Activating FactorMonocyte Secretory Protein JEMyeloid Differentiation-Inducing ProteinNF-kBNF-kappa BNF-kappaBNFKBNK CellsNK T cellNKT cellNatural Killer CellsNatural Killer T cellNeoplasm MetastasisNeuroblastomaNuclear Factor kappa BNuclear Transcription Factor NF-kBOutcomePathway interactionsPatientsPb elementPhenotypePlasmacytoma Growth FactorPlatelet Transforming Growth FactorPlayPopulationPopulation HeterogeneityPreclinical TestingPredispositionProductionProteinsProtocolProtocols documentationPublishingRefractoryRelapseResistanceRho-associated kinaseRho-kinaseRoleSCYA2SIS cytokinesSMAD2STAT3STAT3 geneSecondary NeoplasmSecondary TumorSignal PathwaySmall Inducible Cytokine A2SourceSpecificitySubgroupSusceptibilityT cells for CART-CellsT-LymphocyteTGF BTGF-betaTGF-βTGFbetaTGFβTM-MKRTestingTherapeuticTherapy EvaluationTissue GrowthTranscription Factor NF-kBTransforming Growth Factor betaTransforming Growth Factor-Beta Family GeneTransforming Growth FactorsTranslatingTreatment EfficacyTumor CellTumor Growth FactorsTumor MarkersTumor-associated macrophagesTyrosine-Protein Kinase JAK2WorkXenograftXenograft ModelXenograft procedureXenotransplantationcancer metastasiscancer microenvironmentcancer progressioncell based interventioncell mediated interventioncell mediated therapiescell motilitycell-based therapeuticcell-based therapycellular therapeuticcellular therapychemo-immuno therapychemoattractant cytokinechemoimmunotherapychemokinechemotherapychimeric antigen T cell receptorchimeric antigen receptor (CAR) T cellschimeric antigen receptor Tchimeric antigen receptor T cellschimeric antigen receptor fusion protein T-cellschimeric antigen receptor modified T cellsclinical applicabilityclinical applicationclinical relevanceclinically relevantcombinatorialcytokinecytotoxiccytotoxicitydetermine efficacydevelopmentaldiverse populationsdrug resistantearly clinical trialearly phase clinical trialefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationengineered T cellsepigeneticallyevaluate efficacyexamine efficacygenetically engineered T-cellsheavy metal Pbheavy metal leadheterogeneous populationhigh riskimagingimmune cell infiltrateimmune check pointimmune checkpointimmune microenvironmentimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmunecheckpointimmuno therapyimmunosuppressive microenvironmentimmunosuppressive tumor microenvironmentin vivoin vivo Modelinflammatory environmentinflammatory milieuinhibitorinterferon beta 2intervention efficacykappa B Enhancer Binding Proteinmalignancymesenchymal stromal cellmesenchymal stromal progenitor cellsmesenchymal-derived stem cellsmetabolic fitnessnatural killer T lymphocyteneoplasm progressionneoplasm/cancerneoplastic cellneoplastic progressionneuroblastoma cellnew drug treatmentsnew drugsnew markernew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnovelnovel biomarkernovel drug treatmentsnovel drugsnovel markernovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeuticsnovel therapynuclear factor kappa betaontogenypathwaypopulation diversitypre-clinicalpre-clinical testingpreclinicalprogramsresistance to Drugresistance to therapyresistantresistant to Drugresistant to therapyresponse to therapyresponse to treatmentsocial rolespatial and temporalspatial temporalspatiotemporalsynergismtargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic efficacytherapeutic evaluationtherapeutic resistancetherapeutic responsetherapeutic testingtherapy efficacytherapy resistanttherapy responsethree dimensionalthymus derived lymphocytetransforming growth factors Animal growth regulatorstransgenic T- cellstreatment resistancetreatment responsetreatment responsivenesstumortumor biomarkertumor cell metastasistumor immune microenvironmenttumor microenvironmenttumor progressiontumor specific biomarkertumor-immune system interactionstumorigenicxeno-transplantxeno-transplantationxenograft transplant modelxenotransplant model
Description preview
PROJECT 3 SUMMARY/ABSTRACT
The overall objective of Project 3 is to discover and exploit tumor cell extrinsic mechanisms of therapy resistance
by focusing on the contribution and targeting the immunosuppressive tumor microenvironment (TME) created
by the synergism between tumor-associated macrophages (TAM), cancer-associated fibroblasts (CAF), and…
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