grant
Genome-Wide In Vivo CRISPR Screens in Human T Cells Identify GPCR Pathway Targets to Enhance CAR-T Therapies for Solid Tumors
Organization UNIVERSITY OF CALIFORNIA, SAN FRANCISCOLocation SAN FRANCISCO, UNITED STATESPosted 1 Apr 2026Deadline 31 Mar 2031
NIHUS FederalResearch GrantFY2026AdenosineAdenosine Cyclic Monophosphate-Dependent Protein KinasesAffectAssayAutomobile DrivingB blood cellsB cellB cellsB-CellsB-LymphocytesB-cellBioassayBiological AssayCAR T cell therapyCAR T cellsCAR T therapyCAR modified T cellsCAR-TCAR-TsCD3CD3 AntigensCD3 ComplexCD3 moleculeCD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCRISPRCRISPR editing screenCRISPR screenCRISPR-based screenCRISPR/Cas systemCRISPR/Cas9 screenCatecholaminesCell Communication and SignalingCell FunctionCell IsolationCell LocomotionCell MigrationCell MovementCell PhysiologyCell ProcessCell SegregationCell SeparationCell Separation TechnologyCell SignalingCellular FunctionCellular MigrationCellular MotilityCellular PhysiologyCellular ProcessClustered Regularly Interspaced Short Palindromic RepeatsCuesCyclic AMP-Dependent Protein KinasesDataDevelopmentDistalDysfunctionEngineeringEnvironmentExclusionExhibitsFunctional disorderG Protein-Complex ReceptorG Protein-Coupled Receptor GenesG-Protein-Coupled ReceptorsGPCRGPCR Signaling PathwayGene TargetingGenesGeneticGenetic ScreeningGenetic studyGlutathioneHematologic CancerHematologic MalignanciesHematologic NeoplasmsHematological MalignanciesHematological NeoplasmsHematological TumorHematopoietic CancerHematopoietic Cell TumorHematopoietic MalignanciesHematopoietic NeoplasmsHematopoietic Neoplasms including LymphomasHematopoietic TumorHematopoietic and Lymphoid Cell NeoplasmHematopoietic and Lymphoid NeoplasmsHumanIFN-GammaIFN-gIFN-γIFNGIFNγImmuneImmune InterferonImmunesImmunocompetentImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImpairmentIn VitroInfiltrationInterferon GammaInterferon Type IIIntracellular Communication and SignalingKnock-outKnockoutLigandsMalignant Hematologic NeoplasmMalignant Hematopoietic NeoplasmMediatingMediatorMetabolicMiceMice MammalsMicroscopyModelingModern ManMurineMusOKT3 antigenPKAPathway interactionsPatientsPhysiopathologyPre-Clinical ModelPreclinical ModelsProductionProstaglandinsProstanoidsProtein Kinase ARecoveryResearchResistanceRoleSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSolid NeoplasmSolid TumorSubcellular ProcessSympathinsSystemT cell based immune therapyT cell based therapeuticsT cell based therapyT cell directed therapiesT cell immune therapyT cell immunotherapyT cell infiltrationT cell targeted therapeuticsT cell therapyT cell treatmentT cell-based immunotherapyT cell-based treatmentT cells for CART cellular immunotherapyT cellular therapyT lymphocyte based immunotherapyT lymphocyte based therapyT lymphocyte therapeuticT lymphocyte treatmentT-CellsT-LymphocyteT-cell therapeuticsT-cell transfer therapyT3 AntigensT3 ComplexT3 moleculeT8 CellsT8 LymphocytesTechnologyTestingTreatment EfficacyTumor CellTumor-Infiltrating LymphocytesValidationWorkadoptive T cell transferadoptive T lymphocyte transferadoptive T-cell therapybiological signal transductionblood cancercAMP-Dependent Protein Kinasescancer microenvironmentcancer of bloodcancer of the bloodcell motilitycell sortingchimeric antigen T cell receptorchimeric antigen receptor (CAR) T cell therapychimeric antigen receptor (CAR) T cellschimeric antigen receptor Tchimeric antigen receptor T cell therapychimeric antigen receptor T cellschimeric antigen receptor T therapychimeric antigen receptor fusion protein T-cellschimeric antigen receptor modified T cellsclustered regularly interspaced short palindromic repeats screendevelopmentaldrivingefficacy testingengineered T cellsexhaustionfitnessfunctional genomicsgamma-L-Glu-L-Cys-Glygamma-L-Glutamyl-L-Cysteinylglycinegenetically engineered T-cellsgenome scalegenome wide screengenome-widegenomewidehypoimmunityimmune competentimmune deficiencyimmune suppressionimmune suppressive activityimmune suppressive functionimmunodeficiencyimmunosuppressive activityimmunosuppressive functionimmunosuppressive responseimprovedin vivoinnovateinnovationinnovativeintervention efficacylFN-Gammaleukemia/lymphomaloss of functionlymphoma/leukemiamigrationneoplastic cellnew approachesnext generationnovelnovel approachesnovel strategiesnovel strategypathophysiologypathwaypre-clinicalpreclinicalresistantresponsescreeningscreeningssocial rolesynergismtherapeutic T-cell platformtherapeutic efficacytherapy efficacythymus derived lymphocytetraffickingtranscriptional reprogrammingtransgenic T- cellstranslational opportunitiestranslational potentialtranslational studytumortumor microenvironmentvalidations
Description preview
Background: T cell therapies have been transformative for certain leukemias and lymphomas, however solid
tumors have proven far more difficult due to challenges such as poor infiltration, harsh metabolic environments,
and a myriad of suppressive factors in the tumor microenvironment (TME). Most large-scale genetic screens in
human T cells have…
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