grant
"Off-the-Shelf" iPSC-Derived Regulatory T Cell Immunotherapeutics
Organization UNIVERSITY OF MINNESOTALocation MINNEAPOLIS, UNITED STATESPosted 15 Sept 1997Deadline 30 Apr 2028
NIHUS FederalResearch GrantFY2025AML - Acute Myeloid LeukemiaARAMAcute Myeloblastic LeukemiaAcute Myelocytic LeukemiaAcute Myelogenous LeukemiaAdaptive Immune SystemAddressAdoptive TransferAffectAg Recognition Activation MotifAldesleukin GeneAllogenicAntigensAssayB cell differentiation factorB cell malignancyB cell stimulating factor 2B lymphoid malignancyB-Cell Differentiation FactorB-Cell Differentiation Factor-2B-Cell Stimulatory Factor-2BCDFBSF-2BSF2Basal Transcription FactorBasal transcription factor genesBioassayBiologicalBiological AssayBlood Precursor CellCAR T cellsCAR modified T cellsCAR-TCAR-TsCD19CD19 geneCD4 AntigensCD4 CellsCD4 MoleculeCD4 Positive T LymphocytesCD4 ProteinCD4 ReceptorsCD4 T cellsCD4 helper T cellCD4 lymphocyteCD4+ T-LymphocyteCD4-Positive LymphocytesCD47CD47 AntigenCD47 GlycoproteinCD47 geneCD8CD8 CellCD8 T cellsCD8 lymphocyteCD8 receptorCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCD8BCD8B1CD8B1 geneCell BodyCell Communication and SignalingCell SignalingCellsCellular immunotherapyDataDevelopmentDimerizationDoseDrug usageDrugsDysfunctionEffector CellEnsureEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessExternal DomainExtracellular DomainFOXP3FOXP3 geneForkhead Box P3FrequenciesFunctional disorderGVLGeneral Transcription Factor GeneGeneral Transcription FactorsGenerationsGenesGenomeGerminoblastic SarcomaGerminoblastomaGoalsGvHDHPGFHSC transplantationHematologic CancerHematologic MalignanciesHematologic NeoplasmsHematological MalignanciesHematological NeoplasmsHematological TumorHematopoiesisHematopoieticHematopoietic CancerHematopoietic Cellular Control MechanismsHematopoietic Progenitor CellsHematopoietic Stem Cell TransplantHematopoietic Stem Cell TransplantationHematopoietic stem cellsHepatocyte-Stimulating FactorHomologous Wasting DiseaseHumanHybridoma Growth FactorIFN-beta 2IFNB2IL-2 GeneIL-6IL2IL2 geneIL6 ProteinITAMImmuneImmune SurveillanceImmune responseImmunesImmunologic SurveillanceImmunoreceptor Tyr-Based Activation MotifImmunoreceptor Tyrosine-Based Activation MotifImmunosurveillanceImmunotherapeutic agentIn VitroInnate Immune SystemIntegrin-Associated ProteinInterleukin 2 Precursor GeneInterleukin-2 GeneInterleukin-6Intracellular Communication and SignalingJM2Knock-inLYT3LeadLength of LifeLeukemic progenitor and stem cellLibrariesLigandsLongevityLymphomaLymphoma cellMER6MGI-2MHC ReceptorMacrophageMajor Histocompatibility Complex ReceptorMalignantMalignant - descriptorMalignant Hematologic NeoplasmMalignant LymphomaMediatingMedicationMiceMice MammalsModern ManMurineMusMyeloid CellsMyeloid Differentiation-Inducing ProteinMyeloid ProgenitorMyeloid Progenitor CellsMyeloid Stem CellsMyelosuppressionMφNon-MalignantOKT4 antigenPDX modelPatient derived xenograftPatientsPb elementPeriodicalsPharmaceutical PreparationsPhysiopathologyPlasmacytoma Growth FactorProceduresProductivityProgenitor CellsPropertyProtein DimerizationProteinsReceptor ProteinReceptor SignalingRefractoryRegulatory T-LymphocyteRelapseResistanceRestReticulolymphosarcomaRiskRunt DiseaseSCURFINSTAT3STAT3 geneSignal TransductionSignal Transduction SystemsSignalingSurface Antigen Identified by Monoclonal Antibody 1D8Surface CD4 ReceptorsSystemT cell responseT cells for CART-Cell ActivationT-Cell Antigen ReceptorsT-Cell DevelopmentT-Cell Growth Factor GeneT-Cell OntogenyT-Cell ReceptorT-CellsT-LymphocyteT-Lymphocyte DevelopmentT4 CellsT4 LymphocytesT4 moleculeT8 CellsT8 LymphocytesTCGF GeneTestingThymusThymus GlandThymus ProperThymus Reticuloendothelial SystemTimeToxic effectToxicitiesTranscription Factor Proto-OncogeneTranscription factor genesTregTreg adoptive therapyTreg therapyVHHVHH antibodyacquired immune systemactivate T cellsacute granulocytic leukemiaacute granulocytic leukemia cellacute myeloblastic leukemia cellacute myelocytic leukemia cellacute myelogenous leukemia cellacute myeloid leukemiaacute myeloid leukemia cellacute nonlymphocytic leukemia celladoptive therapy of regulatory T cellsbiologicbiological signal transductionblood cell formationblood cell progenitorblood progenitorblood stem cellblood stem cell transplantationblood-forming stem cellcamelid antibodycamelid based antibodycamelid derived antibodycamelid derived fragmentcamelid heavy chain only Abscamelid immunoglobulincamelid single chain antibodycamelid variable heavy chaincell killingcell typecell-based immunotherapychimeric antigen T cell receptorchimeric antigen receptorchimeric antigen receptor (CAR) T cellschimeric antigen receptor Tchimeric antigen receptor T cellschimeric antigen receptor fusion protein T-cellschimeric antigen receptor modified T cellsclinical efficacycytotoxic CD8 T cellscytotoxic CD8 T lymphocytedesigndesigningdevelopmentaldifferential expressiondifferentially expresseddisease controldisorder controldrug usedrug/agentepigeneticallyexhaustexhaustiongenome editinggenomic editinggraft versus host diseasegraft versus leukemiagraft vs host diseasegraft vs leukemiagraft vs leukemia effectgraft vs leukemia responsegraft vs. host diseasegraft vs. leukemiagraft vs. leukemia effectgraft vs. leukemia responseheavy metal Pbheavy metal leadhelper T lymphocyte markerhematopoietic cell transplantationhematopoietic cellular transplantationhematopoietic progenitorhematopoietic progenitor cell transplantationhematopoietic stem progenitor cellhemopoietichemopoietic progenitorhemopoietic stem cellhiPSChost responsehuman derived pluripotent stem cellhuman iPShuman iPSChuman induced pluripotent cellhuman induced pluripotent stem cellshuman inducible pluripotent stem cellshuman inducible stem cellshuman pluripotent stem cellhumanized micehumanized mouseiPSiPSCiPSCsimmune cell therapyimmune drugsimmune system responseimmune-based therapeuticsimmunogenimmunologic therapeuticsimmunoresponseimmunotherapeuticsimmunotherapy agentimprovedin vivoinduced human pluripotent stem cellsinduced pluripotent cellinduced pluripotent stem cellinducible pluripotent cellinducible pluripotent stem cellinterferon beta 2knockinleukemialeukemia stem/initiating cellsleukemic progenitorleukemic stem cellmouse modelmurine modelmyeloid precursormyeloid stem and progenitor cellnanobodiesnanobodynew approachesnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnonmalignantnovel approachesnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel strategiesnovel strategynovel therapeuticsnovel therapyoverexpressoverexpressionpathophysiologypatient derived xenograft modelperiodicperiodicalperipheral bloodpreventpreventingpromoterpromotorpublic health relevancereceptorreceptor expressionregulatory T-cellsresistantresponserestraintsdAbself-renewself-renewalside effectsingle domain antibodiessite-specific integrationstem cellssynergismthymus derived lymphocytetranscription factortranscriptional differencestranscriptomicstumorvariable heavy chain antibody
Description preview
Abstract We propose to develop nontoxic, tunable off-the-shelf chimeric antigen receptor (CAR) cell-based
immunotherapy to treat acute myeloid leukemia (AML). Murine CD19 CAR CD4 Treg adoptive transfer fully
prevented graft-versus-host disease (GVHD) and eliminated all CD19 lymphoma cells. Surprisingly, the
mechanism was not CD4 Treg mediated…
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