2024
Antigen-specific immune therapy (CNP-106) for treatment of generalised myasthenia gravis: rationale and design of first-in-human randomised controlled trial
Brew S, Frey M, McCarthy D, Elhofy A, Nowak R. Antigen-specific immune therapy (CNP-106) for treatment of generalised myasthenia gravis: rationale and design of first-in-human randomised controlled trial. BMJ Neurology Open 2024, 6: e000836. PMID: 39720510, PMCID: PMC11667273, DOI: 10.1136/bmjno-2024-000836.Peer-Reviewed Original ResearchMyasthenia gravisAntigen-specific immune therapyAntigen-specific T cellsB-cell-mediated autoimmune diseasesImmune tolerance therapyPlacebo-controlled trialGeneralised myasthenia gravisMG subjectsSerious side effectsClinical trial authorisationFood and Drug AdministrationAntigen-specific autoimmunityInstitutional review boardTolerated therapyAChR antibodiesDouble-blindImmune therapyPrimary endpointRandomised controlled trialsSecondary endpointsPathogenic antibodiesT cellsCurrent therapiesAutoimmune diseasesClinical scoresTricky Ts play possum to propagate autoimmune disease.
Panicker A, O'Connor K. Tricky Ts play possum to propagate autoimmune disease. Science Immunology 2024, 9: eadt4136. PMID: 39365872, DOI: 10.1126/sciimmunol.adt4136.Peer-Reviewed Original ResearchConceptsAutoimmune diseasesAntigen-specific T cellsPropagating autoimmune diseasesB cell supportT cellsImmunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection
Cinco I, Napier E, Rhoades N, Davies M, Allison D, Kohama S, Bermudez L, Winthrop K, Fuss C, Spindel E, Messaoudi I. Immunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection. MBio 2024, 15: e00829-24. PMID: 38771046, PMCID: PMC11237422, DOI: 10.1128/mbio.00829-24.Peer-Reviewed Original ResearchConceptsNTM pulmonary diseaseIncreased disease severityNontuberculous mycobacteriaDisease severityBacterial DNAAged animalsAntigen-specific T cellsPulmonary diseaseAssociated with increased disease severityDysregulated macrophage responsePersistence of bacterial DNALack of animal modelsRhesus macaquesSingle-cell RNA sequencingNontuberculous mycobacterial infectionsImmune cell infiltrationRhesus macaque modelBacterial loadAged rhesus macaquesTesting novel therapeuticsRight caudal lobeLower respiratory microbiomeYears of ageMAH infectionMicrobial communities
2023
Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity.
Li X, Huntoon K, Wang Y, Lee D, Dong S, Antony A, Walkey C, Kim B, Jiang W. Radiation Synergizes with IL2/IL15 Stimulation to Enhance Innate Immune Activation and Antitumor Immunity. Molecular Cancer Therapeutics 2023, 23: 330-342. PMID: 37956421, DOI: 10.1158/1535-7163.mct-23-0236.Peer-Reviewed Original ResearchTumor growth inhibitionDendritic cellsAnti-PD-1 checkpoint inhibitorsAntigen-specific T cellsIL-2/ILGreater tumor infiltrationImmune stimulatory mechanismsMurine breast cancer modelAntitumor immune responseCombination of radiotherapyInnate immune activationType I interferon productionImmune-modulatory propertiesIL-15 receptorBreast cancer modelI interferon productionSuperior tumor growth inhibitionGrowth inhibitionInterferon genes (STING) pathwaySystemic immunotherapyWestern blot analysisCheckpoint inhibitorsMetastatic settingAntitumor immunitySurvival benefitIL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive mice
2022
Intramuscular (IM) INO-5401 + INO-9012 with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma.
Reardon D, Brem S, Desai A, Bagley S, Kurz S, De La Fuente M, Nagpal S, Welch M, Hormigo A, Forsyth P, Mandel J, Khagi S, Aiken R, Walbert T, Lieberman F, Portnow J, Battiste J, Gillespie E, Lowy I, Skolnik J. Intramuscular (IM) INO-5401 + INO-9012 with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma. Journal Of Clinical Oncology 2022, 40: 2004-2004. DOI: 10.1200/jco.2022.40.16_suppl.2004.Peer-Reviewed Original ResearchPre-treatment tissueCohort AT cellsLytic potentialAntigen-specific T cellsImmune responsePost-treatment tumor tissuesFlow cytometryMedian OS durationMGMT-unmethylated patientsPD-1 inhibitorsDiagnosed GBM patientsT cell infiltrationAdverse event profileImmune-related markersImmune cell markersRobust immune responseCellular immune responsesWilcoxon rank sum testImmune response suppressionGene expressionPresence of perforinGene expression signaturesRank sum testMedian OS
2016
Quantifying in vivo murine antigen-specific T cell responses without requirement for prior knowledge of antigen identity
Kibbi N, Hong E, Ezaldein H, Hanlon D, Fahmy T, Edelson R. Quantifying in vivo murine antigen-specific T cell responses without requirement for prior knowledge of antigen identity. Transfusion And Apheresis Science 2016, 56: 179-189. PMID: 28007431, DOI: 10.1016/j.transci.2016.11.004.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaExtracorporeal photochemotherapyCalcium fluxT cellsAntigen-specific T cell responsesMalignant cellsPatient-specific tumor antigensOVA-specific T cellsAntigen-specific T cellsAntigen-specific T cell activationControl recipient micePeptide-loaded DCImmune-based therapiesAnti-tumor responseT cell responsesAnti-cancer immunotherapyT-cell lymphomaT cell engagementT cell activationT cell receptor engagementPatient-specific responsesAdoptive transferClinical responseLymph nodesPeripheral blood
2015
Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis
Cao Y, Goods BA, Raddassi K, Nepom GT, Kwok WW, Love JC, Hafler DA. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis. Science Translational Medicine 2015, 7: 287ra74. PMID: 25972006, PMCID: PMC4497538, DOI: 10.1126/scitranslmed.aaa8038.Peer-Reviewed Original ResearchConceptsMyelin-reactive T cellsMultiple sclerosisT cellsHealthy controlsT cell librariesT helper cell 17Antigen-specific T cellsGene signatureMore IL-10More proinflammatory cytokinesAutoreactive T cellsIL-10 productionHuman autoimmune diseasesGranulocyte-macrophage colony-stimulating factorProduction of interferonColony-stimulating factorMyelin antigensTh17 cellsIL-10Inflammatory profileInterleukin-17Proinflammatory cytokinesAutoimmune diseasesDisease progressionHealthy subjectsNLRP3 inflammasome controls adipose tissue leukocytosis and inflammation during aging (INM6P.331)
Camell C, Youm Y, Nguyen K, Ravussin A, Spadaro O, Dixit V. NLRP3 inflammasome controls adipose tissue leukocytosis and inflammation during aging (INM6P.331). The Journal Of Immunology 2015, 194: 193.5-193.5. DOI: 10.4049/jimmunol.194.supp.193.5.Peer-Reviewed Original ResearchAge-related inflammationAdipose tissueAged miceAntigen-specific T cellsDistinct inflammatory signatureB cell infiltrationSpecific T cellsOld control miceVisceral adipose tissueIL-1β signalingB cell subpopulationsAT inflammationAT macrophagesInflammatory signatureVisceral adiposityImmune defectsChronic inflammationControl miceInsulin resistanceLymphocyte clustersCell infiltrationImmune cellsMetabolic dysfunctionT cellsAge-induced changes
2013
Germinal Center Formation Controlled by Balancing Between Follicular Helper T Cells and Follicular Regulatory T Cells
Park H, Kim D, Choi J. Germinal Center Formation Controlled by Balancing Between Follicular Helper T Cells and Follicular Regulatory T Cells. Hanyang Medical Reviews 2013, 33: 10-16. DOI: 10.7599/hmr.2013.33.1.10.Peer-Reviewed Original ResearchFollicular helper T cellsFollicular regulatory T cellsGerminal center reactionRegulatory T cellsHelper T cellsT cell helpT cellsB cellsCenter reactionAutoimmune diseasesCell helpT-betBCL-6Antigen-specific T cellsTranscription factor Bcl-6Expression of CXCR5B cell folliclesPeripheral tolerance mechanismsCD4 T cellsMemory B cellsGerminal center formationIsotype class switchingTfh populationTh17 cellsTfh differentiation
2012
The Dual Effects of B Cell Depletion on Antigen-Specific T Cells in BDC2.5NOD Mice
Xiang Y, Peng J, Tai N, Hu C, Zhou Z, Wong FS, Wen L. The Dual Effects of B Cell Depletion on Antigen-Specific T Cells in BDC2.5NOD Mice. The Journal Of Immunology 2012, 188: 4747-4758. PMID: 22490442, PMCID: PMC4361183, DOI: 10.4049/jimmunol.1103055.Peer-Reviewed Original ResearchConceptsB-cell depletionCell depletionT cellsB cellsAntigen-specific T cellsAg-specific T cellsBDC2.5 T cellsDiabetogenic T cellsRegulatory T cellsT cell responsesB-cell reconstitutionB-cell regenerationT-cell phenotypeImmune regulatory functionsFuture clinical protocolsΒ-cell lossMultiple injection protocolsAutoimmune diabetesRituximab therapyCytokine profileDiabetic patientsCell reconstitutionTherapeutic effectPreclinical studiesHuman CD20RAGE Expression in Human T Cells: A Link between Environmental Factors and Adaptive Immune Responses
Akirav EM, Preston-Hurlburt P, Garyu J, Henegariu O, Clynes R, Schmidt AM, Herold KC. RAGE Expression in Human T Cells: A Link between Environmental Factors and Adaptive Immune Responses. PLOS ONE 2012, 7: e34698. PMID: 22509345, PMCID: PMC3324532, DOI: 10.1371/journal.pone.0034698.Peer-Reviewed Original ResearchConceptsHuman immune responseT cellsImmune responseHuman T cellsRAGE expressionAntigen-specific T cellsAdaptive human immune responsesAdaptive immune cellsSpecific T cellsHealthy control subjectsAdaptive immune responsesExpression of RAGELevels of RAGEInnate immune responseAdvanced glycation endproductsActivated T cellsT cell activationIL-17AGlucose controlControl subjectsIL-5Immune cellsGlycation endproductsCell activationPatients
2011
Distinct polyfunctional CD4+ T cell responses to BCG, ESAT-6 and CFP-10 in tuberculous pleurisy
Li L, Qiao D, Li Q, Zhang X, Lao S, Wu C. Distinct polyfunctional CD4+ T cell responses to BCG, ESAT-6 and CFP-10 in tuberculous pleurisy. Tuberculosis 2011, 92: 63-71. PMID: 22154006, DOI: 10.1016/j.tube.2011.11.004.Peer-Reviewed Original ResearchConceptsPleural fluid cellsESAT-6T cellsMedian fluorescence intensityTuberculous pleurisyCFP-10IL-2Effector/effector memory phenotypeAntigen-specific T cellsFrequent extrapulmonary manifestationMtb-specific antigensEffector memory phenotypeT cell responsesCFP-10 peptidesExtrapulmonary manifestationsPolyfunctional CD4Th1 cytokinesTuberculosis infectionMemory phenotypeInflammatory cellsTh1 cellsSpecific antigenLocal controlCell responsesFollowing StimulationWhite Paper on Adoptive Cell Therapy for Cancer with Tumor-Infiltrating Lymphocytes: A Report of the CTEP Subcommittee on Adoptive Cell Therapy
Weber J, Atkins M, Hwu P, Radvanyi L, Sznol M, Yee C, Committee O. White Paper on Adoptive Cell Therapy for Cancer with Tumor-Infiltrating Lymphocytes: A Report of the CTEP Subcommittee on Adoptive Cell Therapy. Clinical Cancer Research 2011, 17: 1664-1673. PMID: 21325070, DOI: 10.1158/1078-0432.ccr-10-2272.Peer-Reviewed Original ResearchConceptsAdoptive T-cell therapyTumor-infiltrating lymphocytesAdoptive cell therapyInterleukin-2TIL therapyClinical trialsRandomized phase II/III clinical trialsExpansion of TILTumor antigen-specific T cellsHigh-dose IL-2Phase II/III clinical trialsHigh-dose interleukin-2Autologous tumor-infiltrating lymphocytesLonger progression-free survivalPhase II/IIIAntigen-specific T cellsCell therapyT cell-based therapiesTIL infusion productsClinical response rateNonrandomized clinical trialProgression-free survivalStage IV melanomaMetastatic melanoma patientsT-cell therapy
2009
On-Chip Activation and Subsequent Detection of Individual Antigen-Specific T Cells
Song Q, Han Q, Bradshaw EM, Kent SC, Raddassi K, Nilsson B, Nepom GT, Hafler DA, Love JC. On-Chip Activation and Subsequent Detection of Individual Antigen-Specific T Cells. Analytical Chemistry 2009, 82: 473-477. PMID: 20000848, PMCID: PMC2828941, DOI: 10.1021/ac9024363.Peer-Reviewed Original ResearchConceptsAntigen-specific T cellsAntigen-specific CD4T cellsAntigen-specific mannerType 1 diabetesMajor histocompatibility complex receptorIndividual CD4Multiple sclerosisAutoimmune diseasesPrimary T cellsCD4Subnanoliter wellsClinical samplesNumber of cellsComplex receptorSubsequent assessmentHuman tissuesCellsChip activationVivoActivationSclerosisDiabetesCytokinesDiseaseParicalcitol (19-nor-1,25-dihydroxyvitamin D2) and calcitriol (1,25-dihydroxyvitamin D3) exert potent immunomodulatory effects on dendritic cells and inhibit induction of antigen-specific T cells
Sochorová K, Budinský V, Rožková D, Tobiasová Z, Dusilová-Sulková S, Špíšek R, Bartůňková J. Paricalcitol (19-nor-1,25-dihydroxyvitamin D2) and calcitriol (1,25-dihydroxyvitamin D3) exert potent immunomodulatory effects on dendritic cells and inhibit induction of antigen-specific T cells. Clinical Immunology 2009, 133: 69-77. PMID: 19660988, DOI: 10.1016/j.clim.2009.06.011.Peer-Reviewed Original ResearchConceptsAntigen-specific T cellsDendritic cellsT cellsVDR agonistsImmunomodulatory effectsChronic immune-mediated inflammatory diseaseEnd-stage renal disease patientsImmune-mediated inflammatory diseasesImmunomodulatory activityVitamin D receptor activatorsRenal disease patientsImmature dendritic cellsRisk of atherosclerosisPathogenesis of atherosclerosisPotent immunomodulatory effectsToll-like receptorsBioactive IL-12Functional TregsIL-12DC differentiationCalcium resorptionDisease patientsHypercalcemic effectInflammatory diseasesImmunomodulatory potencyCyclophosphamide resets dendritic cell homeostasis and enhances antitumor immunity through effects that extend beyond regulatory T cell elimination
Radojcic V, Bezak K, Skarica M, Pletneva M, Yoshimura K, Schulick R, Luznik L. Cyclophosphamide resets dendritic cell homeostasis and enhances antitumor immunity through effects that extend beyond regulatory T cell elimination. Cancer Immunology, Immunotherapy 2009, 59: 137-148. PMID: 19590872, PMCID: PMC3103867, DOI: 10.1007/s00262-009-0734-3.Peer-Reviewed Original ResearchConceptsDendritic cell homeostasisAntitumor immunityT cellsLow-dose total body irradiationTumor antigen-specific T cellsAnti-CD25 monoclonal antibodyHematopoietic stem cell supportAntigen-specific T cellsUntreated tumor-bearing animalsTumor-infiltrating DCsExpansion of TregsRegulatory T cellsStem cell supportTotal body irradiationT cell responsesLess IL-10More IL-12Tumor-bearing animalsT cell eliminationCell homeostasisDC turnoverTreg depletionImmunotherapeutic strategiesIL-10Body irradiation
2002
Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ
Constant SL, Brogdon JL, Piggott DA, Herrick CA, Visintin I, Ruddle NH, Bottomly K. Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ. Journal Of Clinical Investigation 2002, 110: 1441-1448. PMID: 12438442, PMCID: PMC151814, DOI: 10.1172/jci16109.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntranasalAnimalsAntigen PresentationAntigen-Presenting CellsAntigens, ProtozoanCD4-Positive T-LymphocytesCell DifferentiationCell MovementCytokinesInterleukin-10Interleukin-6Leishmania majorLungLymph NodesLymphotoxin-alphaMiceMice, Inbred C57BLMice, KnockoutTh1 CellsTh2 CellsConceptsAntigen-presenting cellsTh2 T cell differentiationT cell primingT cell differentiationCell primingAntigen-loaded antigen-presenting cellsLung antigen-presenting cellsPulmonary antigen-presenting cellsResident antigen-presenting cellsPreferential primingAntigen-specific T cellsSecondary lymphoid organsTh2-dominated responsesTh1 responseAntigen exposureIL-10Th2 typeAntigen uptakeIL-6Lung microenvironmentLymphoid organsTh2 cellsIntranasal deliveryLung tissueAirway epithelium
2000
Paradoxical inhibition of T-cell function in response to CTLA-4 blockade; heterogeneity within the human T-cell population
Anderson D, Bieganowska K, Bar-Or A, Oliveira E, Carreno B, Collins M, Hafler D. Paradoxical inhibition of T-cell function in response to CTLA-4 blockade; heterogeneity within the human T-cell population. Nature Medicine 2000, 6: 211-214. PMID: 10655112, DOI: 10.1038/72323.Peer-Reviewed Original ResearchConceptsCTLA-4 blockadeT cell populationsCTLA-4T cellsMonoclonal antibodiesB7-1B7-2Immune responseCytotoxic T-lymphocyte antigen-4Whole T cell populationsT-lymphocyte antigen-4Antigen-specific T cellsT cell activation stateHuman T cell populationsT cell functionT cell receptor signalsCo-stimulatory signalsDifferent T cellsT cell stimulationEffect of B7T cell activationActivation stateT cell receptorHuman T cellsFab fragmentsLymphotoxin in inflammation and lymphoid organ development: Variations on a theme
Ruddle N. Lymphotoxin in inflammation and lymphoid organ development: Variations on a theme. Progress In Inflammation Research 2000, 83-88. DOI: 10.1007/978-3-0348-8468-6_8.Peer-Reviewed Original ResearchAutoimmune diseasesLymphoid organsLymphoid organ developmentT cellsTarget organsAntigen-specific T cellsAdditional T cellsLocal lymphoid organsTertiary lymphoid organsConsequence of inflammationLymphoid neogenesisClinical relapseAutoimmune inflammationLocal target organLymphoid tissueInflammatory reactionB cellsInflammationTransgenic miceTissue damageDiseaseTNF familyOrgansUnrelated moleculesOrgan development
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