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 treatmentCooperative 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 cells