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Therapeutic Mechanism of CD47 Blockade in Suppressing Melanoma Metastasis
Organization CEDARS-SINAI MEDICAL CENTERLocation LOS ANGELES, UNITED STATESPosted 20 Apr 2020Deadline 31 Mar 2026 โ ๏ธ
NIHUS FederalResearch GrantFY2025Active OxygenAffectAnti-CD47Antigen PresentationAreaAssayAttentionAutomobile DrivingAutoregulationBasal Transcription FactorBasal transcription factor genesBindingBioassayBiochemicalBiologicalBiological AgentBiological AssayBiological ProductsBlocking AntibodiesBody TissuesCD47CD47 AntigenCD47 GlycoproteinCD47 geneCD47-SIRP-alphaCD47-SIRPฮฑCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCas nuclease technologyCell BodyCell Communication and SignalingCell DifferentiationCell Differentiation processCell LineageCell SignalingCell Surface AntigensCell surfaceCell-Mediated Lympholytic CellsCellsChIP SequencingChIP-seqChIPseqChemosensitizationChemosensitization/PotentiationClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyCytolytic T-CellCytotoxic T CellCytotoxic T-LymphocytesDNADataDeoxyribonucleic AcidDetectionDiseaseDisorderFrequenciesGeneral Transcription Factor GeneGeneral Transcription FactorsGeneralized GrowthGoalsGrowthHomeostasisHumanImmuneImmune EvasionImmune RegulatorsImmune SurveillanceImmunesImmunologic SurveillanceImmunological Surface MarkersImmunomodulatorsImmunosurveillanceImmunotherapeutic agentInfiltrationIntegrin-Associated ProteinIntracellular Communication and SignalingMER6MFR geneMFR proteinMYD-1Macrophage ActivationMacrophage Fusion ReceptorMalignant MelanomaMediatingMelanomaMelanoma CellMelanoma MetastasisMelanoma TumorMelanoma patientMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic MelanomaMetastatic NeoplasmMetastatic TumorModern ManMolecularMolecular InteractionMolecular TargetMyelogenousMyeloidMyeloid CellsMyeloid-derived suppressor cellsNeoplasm MetastasisOrganismOxygen RadicalsP84PD 1PD-1PD1PDX modelPTPNS1PTPNS1 genePathogenesisPatient SelectionPatient derived xenograftPatientsPhagocytesPhagocytic CellPhysiologicPhysiologicalPhysiological HomeostasisPotentiationPredictive ValuePro-OxidantsProductionPropertyProtein-Tyrosine Phosphatase, Nonreceptor Type, Substrate 1PublicationsReactive Oxygen SpeciesReceptor ProteinRecurrent diseaseRegimenRegulationRelapsed DiseaseResistance developmentResistant developmentRoleSHP Substrate 1SHPS1SIRP-Alpha-1SIRPAScientific PublicationSecondary NeoplasmSecondary TumorSignal Regulatory Protein, Alpha Type, 1Signal TransductionSignal Transduction SystemsSignalingSurface Antigen Identified by Monoclonal Antibody 1D8Surface AntigensT cell responseT-Cell ProliferationT-CellsT-LymphocyteTeff cellTherapeuticTimeTissue GrowthTissuesTranscription Factor Proto-OncogeneTranscription factor genesTransgenesTumor CellTumor growth in melanomaTyrosine Phosphatase SHP Substrate 1Upregulationadaptive immune responseamebocyteanti-cancerbiologicbiological signal transductionbiologicsbiopharmaceuticalbiotherapeutic agentcancer metastasiscancer microenvironmentcell typecellular differentiationcellular targetingchromatin immunoprecipitation coupled with sequencingchromatin immunoprecipitation followed by sequencingchromatin immunoprecipitation with sequencingchromatin immunoprecipitation-seqchromatin immunoprecipitation-sequencingclinical predictorsclinical relevanceclinical significanceclinically relevantclinically significantdesigndesigningdeveloping resistancedrivingeffector T cellimmune drugsimmune evasiveimmune microenvironmentimmune modulatorsimmune-based therapeuticsimmunologic therapeuticsimmunomodulatory moleculesimmunoregulatorimmunoregulatory moleculesimmunosuppressive microenvironmentimmunosuppressive myeloid cellsimmunosuppressive tumor microenvironmentimmunotherapeuticsimmunotherapy agentin vivoinnate check pointinnate checkpointinnate immune check pointinnate immune checkpointinnate immunity checkpointkiller T cellliving systemmelanocytemelanoma cancer modelmelanoma modelmelanoma tumor modelmyeloid suppressor cellsmyeloid-derived suppressive cellsneoplastic cellnuclear respiratory factorontogenyoverexpressoverexpressionpatient derived xenograft modelpatients suffering from melanomapatients with melanomaprogrammed cell death 1programmed cell death protein 1programmed death 1promoterpromotorreceptorresearch studyresponseresponse to therapyresponse to treatmentsle2social rolesuppressive myeloid cellssystemic lupus erythematosus susceptibility 2therapeutic responsetherapeutically effectivetherapy responsethymus derived lymphocytetranscription factortransgenetreatment responsetreatment responsivenesstumortumor cell metastasistumor growthtumor immune microenvironmenttumor microenvironmenttumor-immune system interactionsvirtual
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PROJECT SUMMARY
The overall goal of this project is to identify molecular regulators enabling immune suppressive properties of
metastatic melanoma and define cell lineages that mediate therapeutic function of CD47 blocking antibodies.
Our central hypothesis is that metastasizing melanoma cells avoid immune recognition by hyperactivating
CD47โฆ
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