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 Research
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 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 Statements
2022
Double knockout CRISPR screen for cancer resistance to T cell cytotoxicity
Park J, Codina A, Ye L, Lam S, Guo J, Clark P, Zhou X, Peng L, Chen S. Double knockout CRISPR screen for cancer resistance to T cell cytotoxicity. Journal Of Hematology & Oncology 2022, 15: 172. PMID: 36456981, PMCID: PMC9716677, DOI: 10.1186/s13045-022-01389-y.Peer-Reviewed Original ResearchConceptsT cell cytotoxicityCell cytotoxicityT cell killingTumor suppressorCancer patientsImmune responseAvailable agentsSurvival analysisClinical patientsCancer treatmentCancer cellsCancer resistanceDirect targetingPotential new conceptCancer mutationsPatientsCell killingNormal samplesResistance pathwaysCellular responsesSuch resistanceCytotoxicityResistance genesHeterotypic vaccination responses against SARS-CoV-2 Omicron BA.2
Fang Z, Peng L, Lucas C, Lin Q, Zhou L, Yang L, Feng Y, Ren P, Renauer PA, Monteiro VS, Hahn AM, Park JJ, Zhou X, Grubaugh N, Wilen C, Chen S. Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2. Cell Discovery 2022, 8: 69. PMID: 35853867, PMCID: PMC9295082, DOI: 10.1038/s41421-022-00435-w.Peer-Reviewed Original ResearchMultiplexed LNP-mRNA vaccination against pathogenic coronavirus species
Peng L, Fang Z, Renauer PA, McNamara A, Park JJ, Lin Q, Zhou X, Dong MB, Zhu B, Zhao H, Wilen CB, Chen S. Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species. Cell Reports 2022, 40: 111160. PMID: 35921835, PMCID: PMC9294034, DOI: 10.1016/j.celrep.2022.111160.Peer-Reviewed Original ResearchConceptsAntibody responseCoronavirus speciesSequential vaccinationSARS-CoVAntigen-specific antibody responsesSARS-CoV-2 DeltaAdaptive immune cellsEffective immune responsePotent antibody responsesCOVID-19 vaccineSARS-CoV-2MRNA vaccine candidatesActivated B cellsSingle-cell RNA sequencing profilesRNA sequencing profilesSimultaneous vaccinationAntibody immunityVaccination scheduleImmune profileImmune cellsImmune responseVaccine candidatesMERS-CoV.Animal modelsB cellsVariant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2
Peng L, Renauer PA, Ökten A, Fang Z, Park JJ, Zhou X, Lin Q, Dong MB, Filler R, Xiong Q, Clark P, Lin C, Wilen CB, Chen S. Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2. Cell Reports Medicine 2022, 3: 100634. PMID: 35561673, PMCID: PMC9040489, DOI: 10.1016/j.xcrm.2022.100634.Peer-Reviewed Original ResearchConceptsImmune responseImmune cell populationsSARS-CoV-2 spikeAssessment of efficacySARS-CoV-2LNP-mRNABreakthrough infectionsCD8 TImmune profilingMRNA vaccinesPotent protectionT lymphocytesNeutralization activityDelta variantAnimal modelsPotent antibodiesRepertoire diversityCell responsesAuthentic virusSystemic increaseVariant lineagesClonal expansionCell populationsCOVID-19Vaccination
2021
Tumor immunology CRISPR screening: present, past, and future
Dong MB, Tang K, Zhou X, Zhou JJ, Chen S. Tumor immunology CRISPR screening: present, past, and future. Trends In Cancer 2021, 8: 210-225. PMID: 34920978, PMCID: PMC8854335, DOI: 10.1016/j.trecan.2021.11.009.Peer-Reviewed Original Research
2019
Systematic 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 cellsPrecise spatio-temporal interruption of regulatory T cell-mediated CD8+ T cell suppression leads to tumor immunity
Zhou X, Zhao S, He Y, Geng S, Shi Y, Wang B. Precise spatio-temporal interruption of regulatory T cell-mediated CD8+ T cell suppression leads to tumor immunity. Cancer Research 2019, 79: canres.1250.2018. PMID: 30254146, DOI: 10.1158/0008-5472.can-18-1250.Peer-Reviewed Original ResearchConceptsTumor-draining lymph nodesRegulatory T cellsT cellsStrong tumor-suppressive effectSphingosine-1-phosphate receptor 1Low systemic side effectsT cell activityT cell suppressionSignificant tumor reductionSystemic side effectsAntitumor immune activationTumor-suppressive effectsDraining lymphMinimal blockadeTreg ablationTreg inhibitionLymph nodesTumor immunityTumor inoculationClinical evidenceImmune activationImmune suppressionTumor reductionCD8Cell suppression
2017
Analysis of immunological mechanisms exerted by HBsAg-HBIG therapeutic vaccine combined with Adefovir in chronic hepatitis B patients
Zhou C, Li C, Gong G, Wang S, Zhang J, Xu D, Guo L, Ren H, Xu M, Xie Q, Pan C, Xu J, Hu Z, Geng S, Zhou X, Wang X, Zhou X, Mi H, Zhao G, Yu W, Wen Y, Huang L, Wang X, Wang B. Analysis of immunological mechanisms exerted by HBsAg-HBIG therapeutic vaccine combined with Adefovir in chronic hepatitis B patients. Human Vaccines & Immunotherapeutics 2017, 13: 1989-1996. PMID: 28665747, PMCID: PMC5612521, DOI: 10.1080/21645515.2017.1335840.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAdjuvants, ImmunologicAdultAntigen-Antibody ComplexCombined Modality TherapyFemaleHepatitis B Surface AntigensHepatitis B VaccinesHepatitis B, ChronicHumansInterleukin-10Interleukin-17Interleukin-2MaleOrganophosphonatesTh1 CellsTh2 CellsTransforming Growth Factor betaTumor Necrosis Factor-alphaYoung AdultConceptsChronic hepatitis B patientsHepatitis B patientsT cellsImmunized groupsB patientsImmunological mechanismsTherapeutic vaccinesHost-specific immune responseIL-2 levelsSero-conversion rateSpecific immune responseEarly inflammatory responseCHB patientsTc17 cellsTreg cellsCytokine profileIL-17AIL-10Saline groupCell CD4More injectionsAdjuvant controlsClinical trialsInflammatory responseNormal salineInduced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage
Geng S, Zhong Y, Zhou X, Zhao G, Xie X, Pei Y, Liu H, Zhang H, Shi Y, Wang B. Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage. Frontiers In Immunology 2017, 8: 663. PMID: 28638384, PMCID: PMC5461288, DOI: 10.3389/fimmu.2017.00663.Peer-Reviewed Original ResearchEffector T cellsLymph nodesT cellsInduced Regulatory T CellsAntigen-specific mechanismsAntigen-specific TregsHilar lymph nodesRegulatory T cellsAirway inflammationSuppression targetsSuppressive capacityAntigen stimulationReceptor expressionPeripheral generationTherapeutic programSame receptorTregsOptimal inhibitionInflammationCellsAsthmaS1P1AllergensReceptors
2015
Herpes Simplex Virus 1 Suppresses the Function of Lung Dendritic Cells via Caveolin-1
Wu B, Geng S, Bi Y, Liu H, Hu Y, Li X, Zhang Y, Zhou X, Zheng G, He B, Wang B. Herpes Simplex Virus 1 Suppresses the Function of Lung Dendritic Cells via Caveolin-1. MSphere 2015, 22: 883-895. PMID: 26018534, PMCID: PMC4519715, DOI: 10.1128/cvi.00170-15.Peer-Reviewed Original ResearchConceptsInducible nitric oxide synthaseDendritic cellsHSV-1 infectionCav-1HSV-1Nitric oxideHerpes simplex virus 1 (HSV-1) infectionLung dendritic cellsSimplex virus 1 infectionLung pathological changesCav-1 knockout miceNitric oxide synthaseVirus-1 infectionWild-type miceHost antiviral responseHerpes simplex virus 1Cav-1 deficiencySimplex virus 1Adoptive transferCaveolin-1Cav-1 knockdownINOS inhibitorOxide synthasePathological changesTherapeutic approaches