2021
A phase 1b study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO).
Dumbrava E, Dougan M, Gupta S, Cappelli L, Katsumoto T, Rahma O, Painter J, Wang Y, Suarez-Almazor M, Reid P, Wesley S, Hafler D, Bingham C, Warner B, Chung L, Ott P, Kluger H, Khosroshahi A, Tawbi H, Sharon E. A phase 1b study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO). Journal Of Clinical Oncology 2021, 39: tps2676-tps2676. DOI: 10.1200/jco.2021.39.15_suppl.tps2676.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsDisease-specific cohortsAutoimmune disordersAdverse eventsAdvanced malignanciesAnti-PD-1/PD-L1 antibodiesPre-existing autoimmune disordersAnti-PD1 monoclonal antibodiesImpact of nivolumabPhase 1b studyKey secondary endpointPhase Ib studySerious adverse eventsDose-limiting toxicityInflammatory bowel diseasePD-L1 antibodiesSeverity IndexSystemic lupus erythematosusDysfunctional immune systemClinical Trials NetworkTissue-based biomarkersSpecific eligibility criteriaICI therapyPrimary endpointSecondary endpoints
2020
A phase Ib study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO).
Ileana Dumbrava E, Suarez-Almazor M, Painter J, Johanns T, Dougan M, Cappelli L, Bingham C, Wang Y, Gupta S, Warner B, Rahma O, Naidoo J, Ott P, Hafler D, Kluger H, Khosroshahi A, Katsumoto T, Kummar S, Sharon E, Tawbi H. A phase Ib study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO). Journal Of Clinical Oncology 2020, 38: tps3158-tps3158. DOI: 10.1200/jco.2020.38.15_suppl.tps3158.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsAnti-PD-1/PD-L1 antibodiesPhase Ib studyPD-L1 antibodiesAutoimmune disordersAdvanced malignanciesDisease-specific cohortsAdverse eventsIb studyPre-existing autoimmune disordersImpact of nivolumabRisk of flareKey secondary endpointSerious adverse eventsBest objective responseDose-limiting toxicityInflammatory bowel diseaseSeverity IndexSystemic lupus erythematosusAnti-PD1 antibodyClinical Trials NetworkTissue-based biomarkersSpecific eligibility criteriaICI therapyCheckpoint inhibitors
2019
TIGIT signaling restores suppressor function of Th1 Tregs
Lucca LE, Axisa PP, Singer ER, Nolan NM, Dominguez-Villar M, Hafler DA. TIGIT signaling restores suppressor function of Th1 Tregs. JCI Insight 2019, 4: e124427. PMID: 30728325, PMCID: PMC6413794, DOI: 10.1172/jci.insight.124427.Peer-Reviewed Original ResearchIL-12Multiple sclerosisHuman autoimmune disordersT-bet expressionProinflammatory cytokine secretionProduction of IFNType 1 diabetesReduced suppressor activitySuppressor functionRepression of AktFOXO1 nuclear localizationTh1 programTIGIT pathwayCoinhibitory receptorsImmunomodulatory therapyTh17 responsesAutoimmune disordersAutoimmune diseasesSuppressor defectCytokine secretionTregsTIGITProtective effectFunctional inhibitionAkt pathway
2011
An Innate Role for IL-17
Dominguez-Villar M, Hafler DA. An Innate Role for IL-17. Science 2011, 332: 47-48. PMID: 21454778, DOI: 10.1126/science.1205311.Peer-Reviewed Original ResearchConceptsImmune responseImmune dysregulation polyendocrinopathyAbnormal immune responseRegulatory immune cellsRegulatory T cellsHuman autoimmune disordersCytokine interleukin-17Normal immune responseTranscription factor Foxp3IL-17Interleukin-17Autoimmune disordersAutoimmune diseasesImmune cellsImmune system processFOXP3 geneFactor Foxp3T cellsImmune systemFungal infectionsGenetic mutationsHuman genetic mutationsCytokinesInfectionCell types
2009
Soluble IL-2RA Levels in Multiple Sclerosis Subjects and the Effect of Soluble IL-2RA on Immune Responses
Maier LM, Anderson DE, Severson CA, Baecher-Allan C, Healy B, Liu DV, Wittrup KD, De Jager PL, Hafler DA. Soluble IL-2RA Levels in Multiple Sclerosis Subjects and the Effect of Soluble IL-2RA on Immune Responses. The Journal Of Immunology 2009, 182: 1541-1547. PMID: 19155502, PMCID: PMC3992946, DOI: 10.4049/jimmunol.182.3.1541.Peer-Reviewed Original ResearchConceptsMultiple sclerosisIL-2 receptorMS subjectsHealthy controlsOrgan-specific autoimmune disordersChronic systemic inflammationType 1 diabetesT cell proliferationMultiple sclerosis subjectsStrong genetic factorIL-2 signalingSIL-2RaSystemic inflammationAutoimmune disordersImmunological perturbationsAutoimmune diseasesIL-2RAControl subjectsMS casesSerum concentrationsDisease onsetSpecific allelic variantsImmune responseAggressive formDisease riskIL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production
Maier LM, Lowe CE, Cooper J, Downes K, Anderson DE, Severson C, Clark PM, Healy B, Walker N, Aubin C, Oksenberg JR, Hauser SL, Compston A, Sawcer S, , De Jager PL, Wicker LS, Todd JA, Hafler DA. IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production. PLOS Genetics 2009, 5: e1000322. PMID: 19119414, PMCID: PMC2602853, DOI: 10.1371/journal.pgen.1000322.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT1D subjectsSoluble interleukin-2 receptor productionSoluble interleukin-2 receptorOrgan-specific autoimmune disordersHealthy control subjectsInterleukin-2 receptorType 1 diabetesHuman leukocyte antigen (HLA) complexMS risk genesAutoimmune disordersControl subjectsAutoimmunity riskHealthy controlsIL2RA regionType 1Autoimmune lociRisk allelesReceptor productionCandidate gene association studiesAntigen complexGene association studiesAssociation studiesT1D.Sclerosis
2001
CD4+CD25high Regulatory Cells in Human Peripheral Blood
Baecher-Allan C, Brown J, Freeman G, Hafler D. CD4+CD25high Regulatory Cells in Human Peripheral Blood. The Journal Of Immunology 2001, 167: 1245-1253. PMID: 11466340, DOI: 10.4049/jimmunol.167.3.1245.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAntigens, CDAntigens, DifferentiationB7-1 AntigenB7-H1 AntigenBlood ProteinsCD4 AntigensCD4-Positive T-LymphocytesCells, CulturedCoculture TechniquesCTLA-4 AntigenHLA-DR AntigensHumansImmunoconjugatesImmunosuppressive AgentsInterleukin-2KineticsLeukocyte Common AntigensLymphocyte ActivationLymphocyte CountMembrane GlycoproteinsPeptidesReceptors, Antigen, T-CellReceptors, Interleukin-2RNA, MessengerSignal TransductionT-Lymphocyte SubsetsConceptsRegulatory T cellsRegulatory cellsT cellsPD-1/PD-L1Regulatory CD4 T cellsAnti-CD3 stimulusCD4 T cellsHuman autoimmune disordersMultiorgan autoimmune diseasePeripheral lymphoid tissuesRegulatory cell functionIL-2 receptorPD-L1 receptorCirculation of humansHuman peripheral bloodContact-dependent mannerNeonatal day 3B7 pathwayPD-L1Regulatory populationAutoimmune disordersAutoimmune diseasesPeripheral bloodResponder cellsIL-2
2000
Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis
Duda PW, Schmied MC, Cook SL, Krieger JI, Hafler DA. Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. Journal Of Clinical Investigation 2000, 105: 967-976. PMID: 10749576, PMCID: PMC377485, DOI: 10.1172/jci8970.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SequenceCell DivisionCells, CulturedCross ReactionsEpitopes, T-LymphocyteFemaleGlatiramer AcetateHumansImmunodominant EpitopesImmunosuppressive AgentsInterferon-gammaInterleukin-5Leukocytes, MononuclearLigandsMaleMiddle AgedMolecular Sequence DataMultiple SclerosisMyelin Basic ProteinMyelin SheathPeptide FragmentsPeptidesTetanus ToxoidTh2 CellsConceptsT cell responsesMultiple sclerosisGlatiramer acetateT cellsAntigen-specific T cell responsesTh2-polarized immune responseCross-reactive T cellsAlters immune functionHuman autoimmune diseasesAcetate inducesCross-reactive responsesT cell receptorT cell linesImmune deviationMost patientsTh2 typeAutoimmune disordersTh2 cytokinesAutoimmune diseasesDaily injectionsIL-13IL-5Th2 cellsHealthy subjectsImmune response
1996
Antigen-specific therapies for the treatment of autoimmune diseases
Hafler D, Weiner H. Antigen-specific therapies for the treatment of autoimmune diseases. 1996, 61-76. DOI: 10.1007/978-3-642-61191-9_6.Peer-Reviewed Original ResearchAntigen-specific therapyInfectious agentsMajor histocompatibility complexAutoimmune disordersAutoimmune diseasesT cellsLocal antigen-presenting cellsOrgan-specific autoimmune diseasesHuman autoimmune disordersAntigen-presenting cellsOrgan-specific proteinsRange of antigensAutoimmune processAutoimmune cascadeHistocompatibility complexDisordersTherapyDiseasePrimary targetCellsVirusOrgansAgentsSuperantigensEtiology