grant
Defining impact of in situ activation of CD40 and type 1 interferon signaling on theTME and systemic T cell immunity in murine models and cancer patients
Organization H. LEE MOFFITT CANCER CTR & RES INSTLocation TAMPA, UNITED STATESPosted 1 May 2024Deadline 30 Apr 2029
NIHUS FederalResearch GrantFY2025AgonistAntitumor ResponseBiopsyBloodBlood Reticuloendothelial SystemBp50CD154 AntigensCD40CD40 LigandCD40-LCD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCDW40CRAdCancer PatientCancer TreatmentCancersCell BodyCell Communication and SignalingCell SignalingCell surfaceCellsCheckpoint inhibitorClinicalClinical ResearchClinical StudyClinical TrialsCross-PrimingCytolysisDendritic CellsDendritic cell activationDevelopmentDoseEngineeringFDA approvedGene TranscriptionGeneralized GrowthGenerationsGenetic TranscriptionGoalsGrowthHIGM1HumanIFNIFNARIFNAR1IFNAR1 geneIMD3ImmuneImmune checkpoint inhibitorImmune mediated therapyImmunesImmunityImmunologically Directed TherapyImmunostimulatory drugImmunotherapyIn SituInflammatoryInjectionsInnate ImmunityInterferonsIntracellular Communication and SignalingKO miceKnock-out MiceKnockout MiceLaboratory StudyLeadLung NeoplasmsLung TumorLysisMGC9013Malignant CellMalignant MelanomaMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant NeoplasmsMalignant TumorMalignant Tumor of the LungMalignant neoplasm of lungMelanomaMelanoma TumorMembraneMemoryMiceMice MammalsModalityModelingModern ManMurineMusNSCLCNSCLC - Non-Small Cell Lung CancerNative ImmunityNatural ImmunityNon-Small Cell Lung CancerNon-Small-Cell Lung CarcinomaNon-Specific ImmunityNonspecific ImmunityNormal CellNull MouseOncolytic virusesPathway interactionsPatientsPb elementPhasePulmonary CancerPulmonary NeoplasmsPulmonary malignant NeoplasmRNA ExpressionRefractoryResearch ResourcesResourcesSignal TransductionSignal Transduction SystemsSignalingSolidSolid NeoplasmSolid TumorStem Cell likeT cell receptor repertoire sequencingT cell receptor sequencingT cell responseT-B Cell Activating MoleculeT-Cell ActivationT-Cell gp39 AntigenT-CellsT-LymphocyteT8 CellsT8 LymphocytesTCR repertoire sequencingTCR sequencingTCR-seqTCRseqTNF-Related Activation ProteinTNFRSF5TNFRSF5 geneTeff cellTestingTherapeuticTissue GrowthToxic effectToxicitiesTranscriptionTumor CellTumor ImmunityTumor Necrosis Factor Ligand Superfamily Member 5Tumor Necrosis Factor Receptor Superfamily Member 5 GeneTumor growth in melanomaUpregulationValidationVeiled CellsViral ActivityViral FunctionViral Physiologyactivate T cellsanti-cancer immunotherapyanti-cancer therapyanti-tumor immunityanti-tumor responseanticancer immunotherapyantitumor immunitybiological signal transductioncancer cellcancer immunitycancer immunotherapycancer microenvironmentcancer therapycancer typecancer-directed therapycell typeclinical developmentconditionally replicating adenovirusconditionally replicative adenovirusdevelopmentaldraining lymph nodeeffector T cellfallsfirst in manfirst-in-humangain of functionheavy metal Pbheavy metal leadimmune activatorimmune check point inhibitorimmune stimulatory agentimmune stimulatory drugimmune stimulatory therapeuticimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based cancer therapiesimmune-based therapiesimmune-based treatmentsimmuno therapyimmunostimulatory agentsimmunostimulatory biologicsimmunotherapy for cancerimmunotherapy of cancerimprovedinsightloss of functionlung cancermalignancymembrane structuremigrationmouse modelmurine modelneo-antigenneo-epitopesneoantigensneoepitopesneoplasm/cancerneoplastic cellnoveloncolytic adenovirusontogenyp50participant enrollmentpathwaypatient enrollmentpre-clinical studypreclinical studyprogenitor capacityprogenitor cell likeprogenitor-likeprogramsregional lymph noderesponsestem cell characteristicsstem-likestemnesssynergismtargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmentthymus derived lymphocytetraffickingtumortumor growthtumor microenvironmentvalidations
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PROJECT SUMMARY
Recent advances in cancer immunotherapies have revolutionized lung cancer treatment paradigms. However,
many patients derive little or no benefit from FDA approved immune checkpoint inhibitors (ICI). A host of clinical
studies have shown that pre-existing tumor-reactive T cells are critically important to achieve benefit from ICI.…
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