grant
Evaluating and Optimizing Novel nSMase2 Inhibitors in the Treatment of Cancers
Organization UNIVERSITY OF CALIFORNIA, SAN FRANCISCOLocation SAN FRANCISCO, UNITED STATESPosted 1 Sept 2024Deadline 31 Aug 2029
NIHUS FederalResearch GrantFY202521+ years old4T1AddressAdultAdult HumanAllogenicB16F10B7-H1Binding ProteinsBioavailabilityBiogenesisBiological AvailabilityBlood PlasmaCD274CT-26CT26Cancer ModelCancer TreatmentCancerModelCancersCanine SpeciesCanis familiarisCarbamatesCell BodyCellsCheckpoint inhibitorClinicalClinical TrialsCommon Rat StrainsCreativenessDataDevelopmentDogsDogs MammalsDoseDrug KineticsDrug PrecursorsDrugsEffectivenessEnzyme GeneEnzymesExhibitsFosteringFutureGeneralized GrowthGeneticGoalsGrowthHealthHeterograftHeterologous TransplantationHigh Throughput AssayHumanIL-15IL15IL15 ProteinImmuneImmune checkpoint inhibitorImmune infiltratesImmune mediated therapyImmune responseImmunesImmunologically Directed TherapyImmunooncologyImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapyIn VitroInterleukin-15Interleukin-15 PrecursorKnock-outKnockoutKnowledgeLeadLigand Binding ProteinLigand Binding Protein GeneLiverMC-38MC38MGC9721Malignant CellMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant NeoplasmsMalignant TumorMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMeasuresMedicationMetabolicMiceMice MammalsMissionModelingModern ManMolecularMolecular Tumor SuppressionMurineMusNational Institutes of HealthOralOrigin of LifePD-L1PDL-1PatientsPb elementPeptide-MHCPeptide-Major Histocompatibility Protein ComplexPeptide/MHC ComplexPermeabilityPharmaceutical PreparationsPharmacokineticsPhenotypePhysiologic AvailabilityPlasmaPlasma SerumPrimatesPrimates MammalsPro-DrugsProdrugsProductionProgrammed Cell Death 1 Ligand 1Programmed Death Ligand 1PropertyProtein BindingPublic HealthRatRats MammalsRattusResearchResistanceReticuloendothelial System, Serum, PlasmaSafetySolubilitySpecific qualifier valueSpecifiedStructure-Activity RelationshipT-CellsT-LymphocyteTestingTherapeuticTimeTissue GrowthToxic effectToxicitiesTranslationsTransplantationTumor Cell LineTumor ImmunityTumor SuppressionTumor-DerivedUnited States National Institutes of HealthXenograftXenograft procedureXenotransplantationadulthoodanaloganalytical toolanti-cancer therapyanti-tumor immune responseanti-tumor immunityantitumor immunityaqueousassess effectivenessbound proteincancer cellcancer immunitycancer progressioncancer therapycancer typecancer-directed therapycaninecell killingchemical stabilitychemical structure functionclinical translationclinically translatablecreativitydetermine effectivenessdetermine efficacydevelopmentaldomestic dogdrug/agenteffectiveness assessmenteffectiveness evaluationefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationefficacy studyevaluate effectivenessevaluate efficacyexamine effectivenessexamine efficacyexosomeheavy metal Pbheavy metal leadhepatic body systemhepatic organ systemhigh throughput screeninghost responsehuman cancer mouse modelhuman modelhumanized micehumanized mousehypoimmunityimmune cell infiltrateimmune check point inhibitorimmune deficiencyimmune suppressionimmune suppressive activityimmune suppressive functionimmune system responseimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmune-oncologyimmuno oncologyimmuno therapyimmunodeficiencyimmunology oncologyimmunoresponseimmunosuppressive activityimmunosuppressive functionimmunosuppressive responseimprovedin vitro testingin vivoinhibitormalignancymeetingmeetingsmodel of humanmouse modelmurine modelnano-molarnanomolarneoplasm progressionneoplasm/cancerneoplastic progressionnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynovelnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachoncoimmunologyontogenypMHCpre-clinicalpreclinicalprogrammed cell death ligand 1programmed cell death protein ligand 1protein death-ligand 1public health relevancerefractory cancerresistantresistant cancerresponsescaffoldscaffoldingsmall moleculestructure function relationshipthymus derived lymphocytetranslationtransplanttumortumor growthtumor progressionxeno-transplantxeno-transplantation
Description preview
PROJECT ABSTRACT / SUMMARY:
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but many patients fail to respond.
Expanding the response to ICIs is a major goal in immuno-oncology. We and others recently discovered that
blocking exosome biogenesis through the genetic depletion of nSMase2 can overcome resistance to ICIs in…
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