2025
Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs
Dong C, Zhang F, He E, Ren P, Verma N, Zhu X, Feng D, Cai J, Zhao H, Chen S. Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs. Patterns 2025, 6: 101184. DOI: 10.1016/j.patter.2025.101184.Peer-Reviewed Original ResearchParalogous gene pairsParalogous pairsChimeric antigen receptor T cellsResponse to cancer immunotherapyDouble knockoutCancer immunotherapy responseGene pairsCheckpoint blockadeGenome-wide screenImmunotherapy efficacyCancer immunotherapyEnhance immunotherapyImmunotherapy responseImmunotherapy effectT cellsImmunotherapyCancer treatmentIndividual genesCRISPR screensEnrichment analysisParalogsCancerTreatmentCombined targetFunctional significanceAuthor Correction: Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy
Zhang F, Chow R, He E, Dong C, Xin S, Mirza D, Feng Y, Tian X, Verma N, Majety M, Zhang Y, Wang G, Chen S. Author Correction: Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy. Nature Biotechnology 2025, 1-1. PMID: 39901026, DOI: 10.1038/s41587-025-02576-1.Peer-Reviewed Original ResearchMultiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy
Zhang F, Chow R, He E, Dong C, Xin S, Mirza D, Feng Y, Tian X, Verma N, Majety M, Zhang Y, Wang G, Chen S. Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy. Nature Biotechnology 2025, 1-14. PMID: 39820813, DOI: 10.1038/s41587-024-02535-2.Peer-Reviewed Original ResearchAdeno-associated virusTumor microenvironmentImmunosuppressive genesAntitumor efficacyCD8+ T cell infiltrationIn vivo antitumor efficacyCombinatorial cancer immunotherapyImmunosuppressive tumor microenvironmentSyngeneic tumor modelsT cell infiltrationTumor microenvironment remodelingMulti-agent combinationsMultiple tumor typesAntitumor immunityCombinatorial immunotherapyOptimal immunotherapyCancer immunotherapyGene alterationsTumor typesTumor modelReduced neutrophilLiver toxicityShRNA treatmentWhole-transcriptome profilingImmunotherapy
2024
65 High-fidelity enhanced AsCas12a knock-in mice for efficient multiplexed gene editing, disease modeling and orthogonal immunogenetics
Tang K, Zhou X, Fang S, Vandenbulcke E, Du A, Shen J, Cao H, Zhou J, Chen K, Xin S, Zhou L, Lin S, Majety M, Lin X, Lam S, Chow R, Bai S, Nottoli T, Booth C, Liu C, Dong M, Chen S. 65 High-fidelity enhanced AsCas12a knock-in mice for efficient multiplexed gene editing, disease modeling and orthogonal immunogenetics. 2024, a72-a72. DOI: 10.1136/jitc-2024-sitc2024.0065.Peer-Reviewed Original ResearchSingle-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission
Bai Z, Feng B, McClory S, de Oliveira B, Diorio C, Gregoire C, Tao B, Yang L, Zhao Z, Peng L, Sferruzza G, Zhou L, Zhou X, Kerr J, Baysoy A, Su G, Yang M, Camara P, Chen S, Tang L, June C, Melenhorst J, Grupp S, Fan R. Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission. Nature 2024, 634: 702-711. PMID: 39322664, PMCID: PMC11485231, DOI: 10.1038/s41586-024-07762-w.Peer-Reviewed Original ResearchChimeric antigen receptorChimeric antigen receptor T cellsT cellsIL-4CAR T-cell dysfunctionChimeric antigen receptor T-cell productsCAR-T cell persistenceProteomic profiling of seraCAR-T cellsT cell persistenceT-cell therapyLong-term remissionT cell dysfunctionCAR-T productsType 2 cytokinesAntigen-specific activationT cell productionAssociated with patientsType 2 cellsDysfunctional subsetPotential therapeutic strategyCellular immunotherapyLeukemia remissionPatients relapseType 2 functionsCAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors
Peng L, Sferruzza G, Yang L, Zhou L, Chen S. CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors. Cellular & Molecular Immunology 2024, 21: 1089-1108. PMID: 39134804, PMCID: PMC11442786, DOI: 10.1038/s41423-024-01207-0.Peer-Reviewed Original ResearchCAR-natural killerCAR-T cellsCAR-TSolid tumorsHematologic malignanciesCell therapyChimeric antigen receptor (CAR)-T cell therapyImmuno-suppressive tumor microenvironmentCAR-T cell therapyCellular cancer immunotherapyRelapsed/refractory hematologic malignanciesCAR-NK cellsTumor traffickingAdoptive immunotherapyCell immunotherapyCellular immunotherapyCancer immunotherapyImmunotherapeutic approachesHLA compatibilityTumor microenvironmentAdult patientsImmunotherapyCombat cancerTumorMalignancyIn vivo AAVâSB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy
Peng L, Renauer P, Sferruzza G, Yang L, Zou Y, Fang Z, Park J, Chow R, Zhang Y, Lin Q, Bai M, Sanchez A, Zhang Y, Lam S, Ye L, Chen S. In vivo AAVâSB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy. Nature Biotechnology 2024, 1-10. PMID: 38918616, PMCID: PMC11668911, DOI: 10.1038/s41587-024-02282-4.Peer-Reviewed Original ResearchPrimary NK cellsTumor-infiltrating NKCAR-NK cellsNK cellsGenetic checkpointsNatural killerChimeric antigen receptor (CAR)-NK cellsHuman primary NK cellsSolid tumor mouse modelNK cell-based immunotherapyIn vivo antitumor efficacyCAR-NK therapyNK cell therapyCell-based immunotherapyNK cell functionTumor mouse modelTumor infiltrationAntitumor efficacyCell therapyCytokine productionEnhanced cytotoxicityMouse modelSingle-cell transcriptomic landscapeClinical potentialCell functionImmunometabolism of CD8+ T cell differentiation in cancer
Shi H, Chen S, Chi H. Immunometabolism of CD8+ T cell differentiation in cancer. Trends In Cancer 2024, 10: 610-626. PMID: 38693002, PMCID: PMC11342304, DOI: 10.1016/j.trecan.2024.03.010.Peer-Reviewed Original ResearchCD8<sup>+</sup> cytotoxic T lymphocytesT cell receptorImmune signalingCD8+ T cell differentiationMediators of tumor immunityTumor antigen recognitionCytotoxic T lymphocytesT cell differentiationTumor-immune interactionsTumor immunityNovel immunotherapiesT lymphocytesIntracellular metabolic pathwaysCo-stimulationAntigen recognitionMetabolic programmingDesign novel immunotherapiesImmunotherapyCentral mediatorsMetabolic landscapePost-transcriptional mechanismsTumorBidirectional regulationSignaling eventsMetabolic processes
2023
The H2Bub1-deposition complex is required for human and mouse cardiogenesis
Barish S, Berg K, Drozd J, Berglund-Brown I, Khizir L, Wasson L, Seidman C, Seidman J, Chen S, Brueckner M. The H2Bub1-deposition complex is required for human and mouse cardiogenesis. Development 2023, 150: dev201899. PMID: 38038666, PMCID: PMC10730087, DOI: 10.1242/dev.201899.Peer-Reviewed Original ResearchStructural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses
Devarkar S, Vetick M, Balaji S, Lomakin I, Yang L, Jin D, Gilbert W, Chen S, Xiong Y. Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses. Cell Reports 2023, 42: 113156. PMID: 37733586, DOI: 10.1016/j.celrep.2023.113156.Peer-Reviewed Original ResearchConceptsMERS-CoV nsp1Translation inhibitionRibosomal subunitÎ-CoVsModest sequence conservationMRNA entry channelEssential pathogenicity factorHost gene expressionHuman 40S ribosomal subunitSARS-CoV-2 nsp1Cryogenic electron microscopySequence conservationNon-structural protein 1Terminal domainPathogenicity factorsStructural basisGene expressionDevelopment of antiviralsNSP1Entry channelProtein 1Potential therapeutic targetSubunitsExtensive interactionsTherapeutic targetFunction and Cryo-EM structures of broadly potent bispecific antibodies against multiple SARS-CoV-2 Omicron sublineages
Ren P, Hu Y, Peng L, Yang L, Suzuki K, Fang Z, Bai M, Zhou L, Feng Y, Zou Y, Xiong Y, Chen S. Function and Cryo-EM structures of broadly potent bispecific antibodies against multiple SARS-CoV-2 Omicron sublineages. Signal Transduction And Targeted Therapy 2023, 8: 281. PMID: 37518189, PMCID: PMC10387464, DOI: 10.1038/s41392-023-01509-1.Peer-Reviewed Original ResearchCTLA-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 techniquesApplications of CRISPR technology in cellular immunotherapy
Zhou X, Renauer P, Zhou L, Fang S, Chen S. Applications of CRISPR technology in cellular immunotherapy. Immunological Reviews 2023, 320: 199-216. PMID: 37449673, PMCID: PMC10787818, DOI: 10.1111/imr.13241.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAAV-mediated delivery of a Sleeping Beauty transposon and an mRNA-encoded transposase for the engineering of therapeutic immune cells
Ye L, Lam S, Yang L, Suzuki K, Zou Y, Lin Q, Zhang Y, Clark P, Peng L, Chen S. AAV-mediated delivery of a Sleeping Beauty transposon and an mRNA-encoded transposase for the engineering of therapeutic immune cells. Nature Biomedical Engineering 2023, 8: 132-148. PMID: 37430157, PMCID: PMC11320892, DOI: 10.1038/s41551-023-01058-6.Peer-Reviewed Original ResearchGene delivery systemsAdeno-associated virusTransgene expressionHigh transgene expressionSleeping Beauty (SB) transposonTransgene deliverySleeping Beauty transposasePluripotent stem cellsSB transposonLentiviral vectorsGenomic integrationEngineering cellsBeauty transposonMinicircle DNATransposon DNABeauty transposaseCell viabilityPermanent integrationStem cellsElectroporation of plasmidsTransgeneChimeric antigen receptorDeliveryElectroporationEngineeringPooled screening with next-generation gene editing tools
Zhou L, Yang L, Feng Y, Chen S. Pooled screening with next-generation gene editing tools. Current Opinion In Biomedical Engineering 2023, 28: 100479. PMID: 38222973, PMCID: PMC10786633, DOI: 10.1016/j.cobme.2023.100479.Peer-Reviewed Original ResearchGene editing toolsEditing toolsFunction of genesShort palindromic repeatsPooled screensPalindromic repeatsGenetic elementsPool of cellsBiological processesPooled screeningGenetic variantsPotential targetRecent advancesGenesRepeatsPlantsSequencingMutationsAgricultural researchTherapeutic interventionsSimultaneous examinationExpressionPotential future directionsCellsPoolImmunogenetic 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 ResearchConceptsCAR 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 deficiencyHuman Gene Age Dating Reveals an Early and Rapid Evolutionary Construction of the Adaptive Immune System
Zhang L, Park J, Dong M, Arsala D, Xia S, Chen J, Sosa D, Atlas J, Long M, Chen S. Human Gene Age Dating Reveals an Early and Rapid Evolutionary Construction of the Adaptive Immune System. Genome Biology And Evolution 2023, 15: evad081. PMID: 37170918, PMCID: PMC10210621, DOI: 10.1093/gbe/evad081.Peer-Reviewed Original ResearchT cell adaptive immunityNew genesPositive selectionRapid gene duplicationEvolution of longevityStrong positive selectionVertebrate immune systemAdaptive immunityAmino acid substitutionsVertebrate lineageGene ageGene duplicationEutherian radiationGene annotationGenome assemblyRapid originationVertebrate speciesPlacental mammalsHuman genesImmunity genesMolecular adaptationsNucleotide sequenceGenetic constructionNegative regulatorInteraction pathwayPolyvalent mRNA vaccination elicited potent immune response to monkeypox virus surface antigens
Fang Z, Monteiro V, Renauer P, Shang X, Suzuki K, Ling X, Bai M, Xiang Y, Levchenko A, Booth C, Lucas C, Chen S. Polyvalent mRNA vaccination elicited potent immune response to monkeypox virus surface antigens. Cell Research 2023, 33: 407-410. PMID: 36879038, PMCID: PMC9988199, DOI: 10.1038/s41422-023-00792-5.Peer-Reviewed Original ResearchMassively parallel knock-in engineering of human T cells
Dai X, Park J, Du Y, Na Z, Lam S, Chow R, Renauer P, Gu J, Xin S, Chu Z, Liao C, Clark P, Zhao H, Slavoff S, Chen S. Massively parallel knock-in engineering of human T cells. Nature Biotechnology 2023, 41: 1239-1255. PMID: 36702900, PMCID: PMC11260498, DOI: 10.1038/s41587-022-01639-x.Peer-Reviewed Original ResearchMachine learning identifies T cell receptor repertoire signatures associated with COVID-19 severity
Park J, Lee K, Lam S, Moon K, Fang Z, Chen S. Machine learning identifies T cell receptor repertoire signatures associated with COVID-19 severity. Communications Biology 2023, 6: 76. PMID: 36670287, PMCID: PMC9853487, DOI: 10.1038/s42003-023-04447-4.Peer-Reviewed Original ResearchConceptsCOVID-19 disease severityT cell effector functionT cell receptor repertoireT cell clonal expansionT cell adaptive immune responsesCell effector functionsCOVID-19 patientsTCR repertoire analysisAdaptive immune responsesCell receptor repertoireCOVID-19 severityCOVID-19 infectionCell clonal expansionNF-kB signalingSARS-CoV-2TCR repertoireHealthy donorsImmune responseAntiviral immunityEffector functionsViral infectionHost responseDisease severityReceptor repertoireTCR sequences
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