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, DOI: 10.1038/s41590-023-01571-5.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptCell Line, TumorCTLA-4 AntigenCytokinesImmunotherapy, AdoptiveReceptors, Antigen, T-CellReceptors, Chimeric AntigenT-LymphocytesConceptsCytoplasmic tailSingle-cell RNA sequencingRNA sequencingC-terminusTail fusionCell engineering techniquesAntigen receptorFurther characterizationCytometry analysisSurface expressionCAR functionLow surface expressionCellsUnique strategyT cellsPowerful therapeuticsFusionEndocytosisLeukemia modelTerminusTailSequencingPhenotypeReduced activationEngineering techniquesImmunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function.
Renauer P, Park J, Bai M, Acosta A, Lee W, Lin G, Zhang Y, Dai X, Wang G, Errami Y, Wu T, Clark P, Ye L, Yang Q, Chen S. Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function. Cancer Immunology Research 2023, 11: 1068-1084. PMID: 37253111, PMCID: PMC10527769, DOI: 10.1158/2326-6066.cir-22-0565.Peer-Reviewed Original ResearchMeSH KeywordsHumansImmunogeneticsImmunotherapy, AdoptiveMetabolomicsNeoplasmsT-LymphocytesTumor MicroenvironmentConceptsCAR T cellsHER2-specific CAR T cellsT cellsTumor microenvironmentChimeric antigen receptor T cellsT cell-based immunotherapyAntigen receptor T cellsCD19-specific chimeric antigen receptor (CAR) T cellsCAR T-cell therapyCell-based immunotherapyReceptor T cellsT-cell therapyVivo colorectal cancer modelsColorectal cancer modelT cell functionT cell metabolismTumor infiltrationEvasion mechanismsImmunosuppressive metaboliteImmune evasionCancer modelImmunologic analysisCD19-specificUnfavorable tumor microenvironmentPDK1 deficiency
2022
Genome Engineering for Next-Generation Cellular Immunotherapies
Park JJ, Lee KAV, Lam SZ, Tang K, Chen S. Genome Engineering for Next-Generation Cellular Immunotherapies. Biochemistry 2022, 62: 3455-3464. PMID: 35930700, PMCID: PMC11320893, DOI: 10.1021/acs.biochem.2c00340.Peer-Reviewed Original ResearchMeSH KeywordsCytokinesGene EditingHumansImmunotherapyImmunotherapy, AdoptiveNeoplasmsReceptors, Antigen, T-CellTumor MicroenvironmentConceptsGenome engineeringCellular immunotherapySynthetic biology approachesKnockout of genesGenome engineering approachesGenetic screening approachCell therapyNK cell therapyCAR-NK cellsBiology approachHost-graft interactionsNovel target discoveryLong-term persistenceImmune cell typesCRISPR-CasFuture therapeutic developmentTarget discoveryGenetic modificationCell typesAllogeneic contextTumor effect
2019
In 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 killing