2024
MHC class I and II-deficient humanized mice are suitable tools to test the long-term antitumor efficacy of immune checkpoint inhibitors and T-cell engagers
Eguren-Santamaria I, de Piérola E, Camps G, Martín-Muñoz P, Campos M, Cuculescu D, Aguilera-Buenosvinos I, López I, Salido-Vallejo R, Alexandru R, De Andrea C, Álvarez-Gigli L, Berraondo P, Melero I, Sanmamed M. MHC class I and II-deficient humanized mice are suitable tools to test the long-term antitumor efficacy of immune checkpoint inhibitors and T-cell engagers. Journal For ImmunoTherapy Of Cancer 2024, 12: e008516. PMID: 39244214, PMCID: PMC11381650, DOI: 10.1136/jitc-2023-008516.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsHuman peripheral blood mononuclear cellsT-cell engagersNSG miceMajor histocompatibility complexSevere XGVHDImmunodeficient miceAntitumor effectTumor rejectionImmunotherapy agentsAntitumor activityAntitumor efficacy of immune checkpoint inhibitorsEfficacy of immune checkpoint inhibitorsHT29 human colon carcinoma cellsLong-term antitumor efficacyDevelopment of cancer immunotherapyAdministration of nivolumabImmune checkpoint inhibitorsCancer immunotherapy agentsT cell clonesHuman colon carcinoma cellsAlanine aminotransferase levelsMajor histocompatibility complex class IBlood mononuclear cellsHuman immune cells
2022
RAGE antagonism with azeliragon improves xenograft rejection by T cells in humanized mice.
Joshi AA, Wu Y, Deng S, Preston-Hurlburt P, Forbes JM, Herold KC. RAGE antagonism with azeliragon improves xenograft rejection by T cells in humanized mice. Clinical Immunology 2022, 245: 109165. PMID: 36257528, DOI: 10.1016/j.clim.2022.109165.Peer-Reviewed Original ResearchConceptsXenograft rejectionIL-17AHumanized miceIL-1βT cellsImmune responseRAGE antagonistsAdaptive human immune responsesPD-1 expressionSkin graft rejectionHuman immune cell responsesImmune cell responsesHuman immune responseHuman immune cellsInnate immune responseAdvanced glycation endproductsInhibition of pathwaysSmall molecule antagonistsMultiple inflammatory processesAZ therapyRAGE antagonismGraft rejectionIL-23Serum levelsMedian time
2020
Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans
Hu Y, Ranganathan M, Shu C, Liang X, Ganesh S, Osafo-Addo A, Yan C, Zhang X, Aouizerat BE, Krystal JH, D’Souza D, Xu K. Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Scientific Reports 2020, 10: 3450. PMID: 32103029, PMCID: PMC7044203, DOI: 10.1038/s41598-020-59827-1.Peer-Reviewed Original ResearchConceptsSpecific genesCell type-specific genesGene expressionSingle-cell transcriptomic profilingCell typesGene expression correlationsAlters gene expressionTranscriptome mappingTranscriptomic profilingExpression correlationEnrichment analysisCommon genesImportant medical implicationsSignificant genesGenesMajor immune cell typesCell proliferationImmune cell typesImmune responseCell toxicityMedical implicationsCellsImportant insightsExpressionHuman immune cells
2017
Microbiota control immune regulation in humanized mice
Gülden E, Vudattu NK, Deng S, Preston-Hurlburt P, Mamula M, Reed JC, Mohandas S, Herold BC, Torres R, Vieira SM, Lim B, Herazo-Maya JD, Kriegel M, Goodman AL, Cotsapas C, Herold KC. Microbiota control immune regulation in humanized mice. JCI Insight 2017, 2: e91709. PMID: 29093268, PMCID: PMC5752290, DOI: 10.1172/jci.insight.91709.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAntibodies, AntinuclearAntibodies, Monoclonal, HumanizedAutoimmune DiseasesB7-2 AntigenCD11b AntigenCD11c AntigenCD3 ComplexCD8-Positive T-LymphocytesCytokinesDisease Models, AnimalGastrointestinal MicrobiomeGastrointestinal TractGraft RejectionHumansImmunosuppressive AgentsImmunotherapyInterferon-gammaInterleukin-10Interleukin-27Leukocytes, MononuclearMiceMice, KnockoutMucous MembraneSkin TransplantationSTAT5 Transcription FactorT-LymphocytesTransplantation, HeterologousConceptsT cellsIL-10Humanized miceHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsIL-27 expressionIL-10 levelsAnti-nuclear antibodiesEffector T cellsLevels of IFNCentral memory cellsLess IL-10Markers of efficacyBlood mononuclear cellsExpression of CD86Immune regulatory pathwaysIL-10 inductionHuman immune cellsHuman stool samplesImmunosuppressive medicationsIL-27Xenograft rejectionImmune therapyMononuclear cellsAntibiotic treatmentNeutralization of Pathogenic Fungi with Small‐Molecule Immunotherapeutics
Chirkin E, Muthusamy V, Mann P, Roemer T, Nantermet P, Spiegel D. Neutralization of Pathogenic Fungi with Small‐Molecule Immunotherapeutics. Angewandte Chemie 2017, 129: 13216-13220. DOI: 10.1002/ange.201707536.Peer-Reviewed Original ResearchImportant public health concernNovel therapeutic approachesHuman immune cellsSystemic fungal infectionsPublic health concernAntibody-recruiting moleculesFungal illnessImmune cellsNew antifungal agentsTreatment strategiesTherapeutic approachesEndogenous antibodiesRelevant functional assaysFungal infectionsHealth concernFunctional assaysAntifungal agentsNon-peptidic small moleculesC. albicans cellsCandida albicansCellsBiological evaluationAlbicans cellsImmunotherapeuticsIllnessNeutralization of Pathogenic Fungi with Small‐Molecule Immunotherapeutics
Chirkin E, Muthusamy V, Mann P, Roemer T, Nantermet PG, Spiegel DA. Neutralization of Pathogenic Fungi with Small‐Molecule Immunotherapeutics. Angewandte Chemie International Edition 2017, 56: 13036-13040. PMID: 28793176, DOI: 10.1002/anie.201707536.Peer-Reviewed Original ResearchConceptsImportant public health concernNovel therapeutic approachesHuman immune cellsSystemic fungal infectionsPublic health concernAntibody-recruiting moleculesFungal illnessImmune cellsNew antifungal agentsTreatment strategiesTherapeutic approachesEndogenous antibodiesRelevant functional assaysFungal infectionsHealth concernFunctional assaysAntifungal agentsNon-peptidic small moleculesC. albicans cellsCandida albicansCellsBiological evaluationAlbicans cellsImmunotherapeuticsIllness
2012
Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients
Waldron-Lynch F, Henegariu O, Deng S, Preston-Hurlburt P, Tooley J, Flavell R, Herold KC. Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients. Science Translational Medicine 2012, 4: 118ra12. PMID: 22277969, PMCID: PMC4131554, DOI: 10.1126/scitranslmed.3003401.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedCD3 ComplexCell MovementDiabetes Mellitus, Type 1Forkhead Transcription FactorsGastrointestinal TractHumansHypoglycemic AgentsInterleukin-10Intestine, SmallL-SelectinMiceMucous MembraneNatalizumabOligonucleotide Array Sequence AnalysisReceptors, CCR6T-Lymphocytes, RegulatoryConceptsHumanized micePeripheral circulationSmall intestineType 1 diabetes mellitusNovel immunologic mechanismIL-10 expressionTreatment of patientsType 1 diabetesSecondary lymph organsHuman immune cellsT cell migrationMechanism of actionGut-tropicImmunologic mechanismsRegulatory cellsDiabetes mellitusImmune therapyInterleukin-10Immune cellsRegulatory cytokinesClinical trialsPreclinical modelsClinical studiesT cellsHuman hematopoietic stem cells
2010
Human Interleukin-3/Granulocyte Macrophage-Colony Stimulating Factor Knock-In Mice Support Human Myeloid Cell Reconstitution and Human Immune Responses In the Lung.
Willinger T, Rongvaux A, Takizawa H, Eynon E, Stevens S, Manz M, Flavell R. Human Interleukin-3/Granulocyte Macrophage-Colony Stimulating Factor Knock-In Mice Support Human Myeloid Cell Reconstitution and Human Immune Responses In the Lung. Blood 2010, 116: 3789. DOI: 10.1182/blood.v116.21.3789.3789.Peer-Reviewed Original ResearchHuman immune responsePulmonary alveolar proteinosisImmune responseHuman myeloid cellsKI miceCell reconstitutionMyeloid cellsEnhanced systemic inflammatory responseFunctional human immune systemGM-CSFStrong innate immune responseSystemic inflammatory responseInfluenza virus infectionIL-3Human immune cellsInnate immune responseNew mouse modelHuman alveolar macrophagesHuman immune systemGranulocyte-macrophage colonyPAP syndromeHumanized miceAlveolar proteinosisImmune cellsInflammatory response
2009
Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/γc−/−, Balb/c-Rag1−/−γc−/−, and C.B-17-scid/bg immunodeficient mice
Lepus CM, Gibson TF, Gerber SA, Kawikova I, Szczepanik M, Hossain J, Ablamunits V, Kirkiles-Smith N, Herold KC, Donis RO, Bothwell AL, Pober JS, Harding MJ. Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/γc−/−, Balb/c-Rag1−/−γc−/−, and C.B-17-scid/bg immunodeficient mice. Human Immunology 2009, 70: 790-802. PMID: 19524633, PMCID: PMC2949440, DOI: 10.1016/j.humimm.2009.06.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFetal BloodGranulocyte Colony-Stimulating FactorHematopoietic Stem Cell MobilizationHematopoietic Stem Cell TransplantationHematopoietic Stem CellsHemocyaninsHumansHypersensitivity, DelayedImmunoglobulinsInfluenza A Virus, H5N1 SubtypeLiverLymph NodesLymphocyte SubsetsMiceMice, Inbred BALB CMice, Inbred NODMice, KnockoutMice, SCIDRadiation DosageSpleenThymus GlandWhole-Body IrradiationConceptsNOD-scid/Umbilical cord bloodBALB/cHuman fetal liverCord bloodUCB-HSCImmunodeficient miceSecond trimester human fetal liverHematopoietic stem cell preparationsFetal liverTotal human immunoglobulinWhite pulp expansionHumanized mouse modelHematopoietic stem cell engraftmentHuman immune responseHuman immune cellsStem cell engraftmentHuman immune systemHuman T cellsStem cell preparationsDendritic cellsAntigenic challengeDependent antigenPeripheral bloodImmune cellsHuman TRIM Gene Expression in Response to Interferons
Carthagena L, Bergamaschi A, Luna JM, David A, Uchil PD, Margottin-Goguet F, Mothes W, Hazan U, Transy C, Pancino G, Nisole S. Human TRIM Gene Expression in Response to Interferons. PLOS ONE 2009, 4: e4894. PMID: 19290053, PMCID: PMC2654144, DOI: 10.1371/journal.pone.0004894.Peer-Reviewed Original ResearchConceptsTRIM genesTRIM proteinsAntiviral activityGene expressionFamily of proteinsTripartite motif (TRIM) proteinsPrimary human immune cellsAntiviral immune responseGene expression analysisHuman immune cellsHost antiviral activityActivation of macrophagesMonocyte-derived macrophagesHuman primary lymphocytesMotif proteinTripartite architectureExpression analysisImmune cellsImmune responseHIV activityInnate immunityPrimate cellsGenesPrimary lymphocytesProtein
2007
Allelic variant in CTLA4 alters T cell phosphorylation patterns
Maier LM, Anderson DE, De Jager PL, Wicker LS, Hafler DA. Allelic variant in CTLA4 alters T cell phosphorylation patterns. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 18607-18612. PMID: 18000051, PMCID: PMC2141824, DOI: 10.1073/pnas.0706409104.Peer-Reviewed Original ResearchConceptsT cell antigen receptorAllelic variationMemory T cellsAutoimmune diseasesCell antigen receptorT cell signalingT cellsFunctional effectsDisease susceptibility allelesCell signalingPhosphorylation patternPhosphorylation levelsSusceptibility variantsTCR stimulationAllelic variantsHuman immune cellsAntigen receptorGenesImmune cellsHealthy individualsCTLA4 geneCellsSpecific mAbsCTLA4Disease
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