grant
Determinants of toxicity and response to immune checkpoint blockade through integrative profiling of T cell clonal dynamics and plasma cell- free DNA
Organization MAYO CLINIC ROCHESTERLocation ROCHESTER, UNITED STATESPosted 7 Jun 2024Deadline 31 May 2029
NIHUS FederalResearch GrantFY2025AddressAssayAtrophic ArthritisAutoimmune DiseasesB blood cellsB cellB cellsB-CellsB-LymphocytesB-cellBLR1BLR1 geneBenchmarkingBest Practice AnalysisBioassayBiological AssayBiological MarkersBiologyBiopsyBloodBlood PlasmaBlood Plasma CellBlood Reticuloendothelial SystemBody SystemBody TissuesBrittle Diabetes MellitusCD4 CellsCD4 Positive T LymphocytesCD4 T cellsCD4 helper T cellCD4 lymphocyteCD4+ T-LymphocyteCD4-Positive LymphocytesCTLA-4 therapyCTLA-4 treatmentCTLA4 therapyCTLA4 treatmentCXCR-5CXCR5CancersCell BodyCellsCessation of lifeCheckpoint inhibitorClinicalClonal ExpansionCombination immunotherapyCombined Modality TherapyComputational BiologyDNA MethylationDNA methylation profilingDataDeathDecision MakingDermalDevelopmentDysfunctionEcologic SystemsEcological SystemsEcosystemFlow CytofluorometriesFlow CytofluorometryFlow CytometryFlow MicrofluorimetryFlow MicrofluorometryFoundationsFrequenciesFunctional disorderFutureGenesHospital AdmissionHospitalizationHumanIDDMImmuneImmune checkpoint inhibitorImmune mediated therapyImmunesImmunologically Directed TherapyImmunotherapyIncidenceInsulin-Dependent Diabetes MellitusJuvenile-Onset Diabetes MellitusKetosis-Prone Diabetes MellitusKnowledgeLifeLinkLupusLymphatic cellLymphocyteLymphocyticMDR15Machine LearningMalignant MelanomaMalignant NeoplasmsMalignant TumorMeasuresMediatingMedicineMelanomaMelanoma patientMethyl-SeqMethylSeqMethylation sequencingModern ManModernizationMorbidityMorbidity - disease rateMultimodal TherapyMultimodal TreatmentNatureOrganOrgan SystemOutcomePBMCPD-1 antibodyPD1 antibodyPatientsPeripheralPeripheral Blood Mononuclear CellPhysiopathologyPlasmaPlasma CellsPlasma SerumPlasmacytesPlayPredicting RiskProbabilityPublishingReticuloendothelial System, Serum, PlasmaRheumatoid ArthritisRiskSamplingSiteSkinSortingSudden-Onset Diabetes MellitusT-CellsT-LymphocyteT1 DMT1 diabetesT1DT1DMT4 CellsT4 LymphocytesTechnologyTestingTissuesToxic effectToxicitiesType 1 Diabetes MellitusType 1 diabetesType I Diabetes MellitusValidationVisceralaCTLA-4aCTLA-4 antibodiesaCTLA-4 therapyaCTLA-4 treatmentaCTLA4aCTLA4 therapyaPD-1aPD1anti programmed cell death 1anti-CTLA-4anti-CTLA-4 antibodiesanti-CTLA-4 therapyanti-CTLA-4 treatmentanti-CTLA4anti-CTLA4 antibodiesanti-CTLA4 therapyanti-CTLA4 treatmentanti-PD-1anti-PD-1 Abanti-PD-1 antibodiesanti-PD-1 monoclonal antibodiesanti-PD1anti-PD1 Abanti-PD1 antibodiesanti-PD1 monoclonal antibodiesanti-cancer treatmentanti-programmed cell death protein 1anti-programmed cell death protein 1 antibodiesanti-programmed death-1 antibodyantiPD-1autoimmune conditionautoimmune disorderautoimmune reactivityautoimmunity diseaseautoreactivitybenchmarkbio-markersbiologic markerbiomarkerblood treatmentcell free DNAcell free circulating DNAcheck point blockadecheckpoint blockadeclinical decision-makingclinical practicecohortcombination therapycombinatorial immunotherapycombined modality treatmentcombined treatmentcomputer biologycutaneous lesionsdermal lesiondevelopmentaldual immunotherapyexperienceflow cytophotometryforecasting riskgene signaturesgenetic signaturegenome wide methylationgenomewide methylationglobal methylationhigh dimensionalityimmune check point blockadeimmune check point inhibitorimmune checkpoint blockadeimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmune-mediated adverse eventsimmune-related adverse effectimmune-related adverse eventsimmune-related adverse reactionimmuno therapyimmunotherapy clinical trialsimprovedinnovateinnovationinnovativeinsightinsulin dependent diabetesinsulin dependent type 1juvenile diabetesjuvenile diabetes mellitusketosis prone diabeteslearning activitylearning methodlearning strategieslearning strategyliquid biopsylymph cellmachine based learningmachine learning based methodmachine learning methodmachine learning methodologiesmalignancymemory CD4 T cellmemory CD4 T lymphocyteminimally invasivemortalitymulti-modal therapymulti-modal treatmentmulti-modalitymultimodalityneoplasm/cancernew technologynovel technologiesorgan developmentorgan growthpathophysiologypatient profilepatients suffering from melanomapatients with melanomaperipheral bloodpersonalization of treatmentpersonalized medicinepersonalized therapypersonalized treatmentplasmocytepredict riskpredict riskspredicted riskpredicted riskspredicting riskspredictive assaypredictive riskpredictive signaturepredictive testpredicts riskprofiles in patientsprospectiveresponseresponse biomarkerresponse markersrheumatic arthritisrisk predictionrisk predictionsscRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingskin lesionthymus derived lymphocytetype I diabetestype one diabetesvalidationsα-CTLA-4α-CTLA4αCTLA-4αCTLA-4 treatmentαCTLA4αPD-1αPD1
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PROJECT SUMMARY
Severe immune-related adverse events (irAEs) occur in up to ~60% of melanoma patients treated
with combination (anti-PD1 / anti-CTLA4) immune checkpoint inhibitors (ICIs), and cause treatment-
related morbidity and mortality. However, the pathophysiology underlying severe irAE development
remains unclear and there is no way in…
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