2023
CTLA-4 tail fusion enhances CAR-T antitumor immunity
Zhou X, Cao H, Fang S, Chow R, Tang K, Majety M, Bai M, Dong M, Renauer P, Shang X, Suzuki K, Levchenko A, Chen S. CTLA-4 tail fusion enhances CAR-T antitumor immunity. Nature Immunology 2023, 24: 1499-1510. PMID: 37500885, PMCID: PMC11344484, DOI: 10.1038/s41590-023-01571-5.Peer-Reviewed Original ResearchConceptsCytoplasmic tailSingle-cell RNA sequencingRNA sequencingC-terminusTail fusionCell engineering techniquesAntigen receptorFurther characterizationCytometry analysisSurface expressionCAR functionLow surface expressionCellsUnique strategyT cellsPowerful therapeuticsFusionEndocytosisLeukemia modelTerminusTailSequencingPhenotypeReduced activationEngineering techniques
2019
Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity
Wang G, Chow RD, Bai Z, Zhu L, Errami Y, Dai X, Dong MB, Ye L, Zhang X, Renauer PA, Park JJ, Shen L, Ye H, Fuchs CS, Chen S. Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity. Nature Immunology 2019, 20: 1494-1505. PMID: 31611701, PMCID: PMC6858551, DOI: 10.1038/s41590-019-0500-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAntigens, NeoplasmCancer VaccinesCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCoculture TechniquesCombined Modality TherapyDependovirusDisease Models, AnimalFemaleGene Expression Regulation, NeoplasticGenetic TherapyGenetic VectorsHEK293 CellsHumansImmunotherapyInjections, IntralesionalLymphocytes, Tumor-InfiltratingMaleMiceNeoplasmsT-Lymphocytes, CytotoxicTumor MicroenvironmentConceptsAntitumor immunityImmune responseCell-based vaccination strategiesElicits potent antitumor immunityEnhanced T cell infiltrationElicit potent immune responsesCurrent immunotherapy modalitiesStrong antitumor immunityAntitumor immune responseT cell infiltrationPotent antitumor immunityPotent immune responsesAntitumor immune signaturesMultiple cancer typesImmune signaturesImmunotherapy modalitiesTreatment modalitiesCell infiltrationVaccination strategiesTumor antigensVirus deliveryTumor microenvironmentImmunotherapyCancer typesCancer treatmentIn vivo CRISPR screening in CD8 T cells with AAV–Sleeping Beauty hybrid vectors identifies membrane targets for improving immunotherapy for glioblastoma
Ye L, Park JJ, Dong MB, Yang Q, Chow RD, Peng L, Du Y, Guo J, Dai X, Wang G, Errami Y, Chen S. In vivo CRISPR screening in CD8 T cells with AAV–Sleeping Beauty hybrid vectors identifies membrane targets for improving immunotherapy for glioblastoma. Nature Biotechnology 2019, 37: 1302-1313. PMID: 31548728, PMCID: PMC6834896, DOI: 10.1038/s41587-019-0246-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCD8-Positive T-LymphocytesCell Line, TumorCRISPR-Cas SystemsDependovirusFemaleGene EditingGlioblastomaHumansImmunotherapy, AdoptiveLymphocyte Activation Gene 3 ProteinMaleMembrane ProteinsMiceN-AcetylglucosaminyltransferasesNeoplasm ProteinsProtein Disulfide-IsomerasesReceptors, Cell SurfaceRNA, Guide, CRISPR-Cas SystemsTransposasesXenograft Model Antitumor AssaysConceptsRNA cassetteMembrane protein targetsPrimary murine T cellsGenetic screening systemSingle-cell sequencingScreen hitsSleeping Beauty (SB) transposonCRISPR screensMembrane proteinsCell sequencingT cellsAdeno-associated virusGenomic integrationMembrane targetsMurine T cellsProtein targetsEfficient geneHuman GBM cellsGene editingT cell receptor transgenic modelGBM cellsBeauty transposonPDIA3T cell-based immunotherapyAntigen-specific killingCooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer
Craig M, Kaveh K, Woosley A, Brown AS, Goldman D, Eton E, Mehta RM, Dhawan A, Arai K, Rahman MM, Chen S, Nowak MA, Goldman A. Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer. PLOS Computational Biology 2019, 15: e1007278. PMID: 31449515, PMCID: PMC6709889, DOI: 10.1371/journal.pcbi.1007278.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationCoculture TechniquesComputational BiologyComputer SimulationCRISPR-Cas SystemsDEAD-box RNA HelicasesDrug Resistance, MultipleDrug Resistance, NeoplasmHumansLung NeoplasmsModels, BiologicalMutationRibonuclease IIIConceptsCancer cellsCell state transitionsWild-type cellsCooperative adaptationNon-small cell lung cancer cellsInterspecies competitionCell lung cancer cellsCRISPR/Drug-sensitive cellsLung cancer cellsNSCLC patient samplesDruggable targetsDrug pressureMutantsFlow cytometry dataPhenotypic heterogeneitySensitive cellsSystematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells
Dong MB, Wang G, Chow RD, Ye L, Zhu L, Dai X, Park JJ, Kim HR, Errami Y, Guzman CD, Zhou X, Chen KY, Renauer PA, Du Y, Shen J, Lam SZ, Zhou JJ, Lannin DR, Herbst RS, Chen S. Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells. Cell 2019, 178: 1189-1204.e23. PMID: 31442407, PMCID: PMC6719679, DOI: 10.1016/j.cell.2019.07.044.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCD8-Positive T-LymphocytesCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCytokinesFemaleHumansImmunologic MemoryImmunotherapyMaleMiceMice, KnockoutNF-kappa BProgrammed Cell Death 1 ReceptorRNA HelicasesRNA, Guide, CRISPR-Cas SystemsTranscriptomeConceptsCRISPR screensTarget discoveryGenome-scale CRISPR screensCD8 TRNA helicase DHX37Vivo CRISPR screensGenetic screenGenome scaleTranscriptomic profilingBiochemical interrogationAntigen-specific CD8 TAnti-tumor immune responseFunctional regulatorTriple-negative breast cancerDHX37Essential roleTim-3PD-1Cytokine productionTumor infiltrationImmunotherapy targetImmunotherapy settingsRegulatorBreast cancerT cellsIn vivo profiling of metastatic double knockouts through CRISPR–Cpf1 screens
Chow RD, Wang G, Ye L, Codina A, Kim HR, Shen L, Dong MB, Errami Y, Chen S. In vivo profiling of metastatic double knockouts through CRISPR–Cpf1 screens. Nature Methods 2019, 16: 405-408. PMID: 30962622, PMCID: PMC6592845, DOI: 10.1038/s41592-019-0371-5.Peer-Reviewed Original Research
2018
Programmable sequential mutagenesis by inducible Cpf1 crRNA array inversion
Chow RD, Kim HR, Chen S. Programmable sequential mutagenesis by inducible Cpf1 crRNA array inversion. Nature Communications 2018, 9: 1903. PMID: 29765043, PMCID: PMC5954137, DOI: 10.1038/s41467-018-04158-z.Peer-Reviewed Original Research
2014
Global microRNA depletion suppresses tumor angiogenesis
Chen S, Xue Y, Wu X, Le C, Bhutkar A, Bell EL, Zhang F, Langer R, Sharp PA. Global microRNA depletion suppresses tumor angiogenesis. Genes & Development 2014, 28: 1054-1067. PMID: 24788094, PMCID: PMC4035535, DOI: 10.1101/gad.239681.114.Peer-Reviewed Original ResearchConceptsUntranslated regionCRISPR/Multiplexed CRISPR/HIF transcriptional activityHypoxia-inducible factor-1Tumor angiogenesisMicroRNA-binding sitesGenome engineeringExpression profilingTranscriptional activityHypoxia responseBalance of angiogenesisHIF transcriptionMicroRNA deficiencyMicroRNAsFIH1Factor 1Angiogenesis genesDeficient angiogenesisAngiogenesisVEGF productionTranscription