grant
Rewiring T cell exhaustion with immune checkpoint blockade therapy
Organization SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTELocation LA JOLLA, UNITED STATESPosted 7 Aug 2024Deadline 31 Jul 2029
NIHUS FederalResearch GrantFY2025AddressAfter CareAfter-TreatmentAftercareAnimalsAntibodiesAntigensAntitumor ResponseAutomobile DrivingB7-H1BindingBloodBlood Reticuloendothelial SystemBlood leukocyteCD152CD152 AntigenCD152 GeneCD162 antigenCD274CD62P AntigensCD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCTLA 4CTLA-4 GeneCTLA4CTLA4 geneCTLA4-TMCancer PatientCancersCell BodyCell Communication and SignalingCell SignalingCellsCharacteristicsCheckpoint inhibitorChronicClinicalClinical Treatment MoabCytotoxic T-Lymphocyte Protein 4Cytotoxic T-Lymphocyte-Associated Antigen 4Cytotoxic T-Lymphocyte-Associated Protein 4Cytotoxic T-Lymphocyte-Associated Serine Esterase-4DevelopmentEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessFrequenciesGMP-140Gene TranscriptionGeneHomologGenerationsGenesGenetic TranscriptionGlycoproteinsGoalsHistologicHistologicallyHistologyHomologHomologous GeneHomologueHumanHuman CloningImmuneImmune checkpoint inhibitorImmune mediated therapyImmune responseImmunesImmunofluorescenceImmunofluorescence ImmunologicImmunologically Directed TherapyImmunotherapyIn VitroIndustryInfectionInflammationIntracellular Communication and SignalingLCM VirusesLCMVLECAM-3LEF Transcription FactorLeadLeukocytesLeukocytes Reticuloendothelial SystemLigandsLymphocytic choriomeningitis virusLymphoid Enhancer FactorMaintenanceMalignant MelanomaMalignant NeoplasmsMalignant TumorMarrow leukocyteMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMediatingMelanomaMelanoma TumorMelanoma patientMiceMice MammalsModern ManMolecular InteractionMonoclonal AntibodiesMurineMusOutcomeP-SelectinP-selectin glycoprotein ligand-1P-selectin ligand proteinPD 1PD-1PD-1 antibodyPD-1 blockadePD-L1PD1PD1 antibodyPD1 blockadePDL-1PSGL-1Pathway interactionsPatient outcomePatient-Centered OutcomesPatient-Focused OutcomesPatientsPb elementPhenotypePlatelet alpha-Granule Membrane ProteinProgrammed Cell Death 1 Ligand 1Programmed Death Ligand 1Progression-Free SurvivalsRNA ExpressionReceptor ProteinRegulationReporterResistanceSamplingSignal TransductionSignal Transduction SystemsSignalingStem Cell likeT Cell FactorT cell differentiationT cell responseT-Cell DevelopmentT-Cell OntogenyT-Cell SubsetsT-CellsT-LymphocyteT-Lymphocyte DevelopmentT-Lymphocyte SubsetsT8 CellsT8 LymphocytesTCF Transcription FactorTeff cellTestingTherapeuticTimeToxic effectToxicitiesTranscriptionTumor CellTumor growth in melanomaUpregulationViral DiseasesVirus DiseasesWhite Blood CellsWhite CellaPD-1aPD1anti programmed cell death 1anti-PD-1anti-PD-1 Abanti-PD-1 antibodiesanti-PD-1 blockadeanti-PD-1 monoclonal antibodiesanti-PD1anti-PD1 Abanti-PD1 antibodiesanti-PD1 blockadeanti-PD1 monoclonal antibodiesanti-programmed cell death protein 1anti-programmed cell death protein 1 antibodiesanti-programmed death-1 antibodyanti-tumor responseantiPD-1biological signal transductioncancer microenvironmentcheck point blockadecheckpoint blockadeclinical translationclinically translatablecytotoxic T-lymphocyte antigen 4developmentaldrivingeffector T cellepigeneticallyexhaustexhaustionheavy metal Pbheavy metal leadhost responsehumanized micehumanized mouseimmune check point blockadeimmune check point inhibitorimmune checkpoint blockadeimmune system responseimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmuno therapyimmunogenimmunoresponseimproved outcomein vivomAbsmalignancymelanoma cancer modelmelanoma modelmelanoma tumor modelmigrationmonoclonal Absmouse modelmurine modelneoplasm/cancerneoplastic cellnovelpathwaypatient oriented outcomespatient responsepatient specific responsepatient subclasspatient subclusterpatient subgroupspatient subpopulationspatient subsetspatient subtypespatients suffering from melanomapatients with melanomapost treatmentpredict responsivenesspredicting responsepreventpreventingprogenitor capacityprogenitor cell likeprogenitor-likeprogrammed cell death 1programmed cell death ligand 1programmed cell death protein 1programmed cell death protein ligand 1programmed death 1protein death-ligand 1receptorresistantresponseresponsive patientself renewing cellself-renewself-renewalsle2stem cell characteristicsstem-likestemnesssynergismsystemic lupus erythematosus susceptibility 2targeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmentthymus derived lymphocytetranslational opportunitiestranslational potentialtreatment effecttumortumor growthtumor microenvironmentviral infectionvirus infectionvirus-induced diseasewhite blood cellwhite blood corpuscleαPD-1αPD1
Description preview
PROJECT SUMMARY
The goal of this project is to determine whether it is possible to promote the development and/or
maintenance of CD8+ T cells that are essential for anti-tumor responses to PD-1 immune checkpoint
blockade (ICB) therapy by targeting PSGL-1 (P-selectin glycoprotein-1). Studies of exhausted CD8 T cells
(TEX) with chronic LCMV…
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