2020
Use of CART cells to selectively target autoantigen-specific T cells for the treatment of autoimmune diabetes
Yu H, Bettini M, Ellis G, Riley J, Collins J, Preston-Hurlburt P, Korah M, Mallone R, Deng S, Wang X, Fremont D, Spiegel D, Cresswell P, Herold K. Use of CART cells to selectively target autoantigen-specific T cells for the treatment of autoimmune diabetes. The Journal Of Immunology 2020, 204: 238.8-238.8. DOI: 10.4049/jimmunol.204.supp.238.8.Peer-Reviewed Original ResearchCART cellsT cellsAutoimmune diabetesCAR constructsHuman antigen-specific CD8Autoantigen-specific T cellsAntigen-specific CD8Pathogenic T cellsPrevious clinical trialsΒ-cell damageChimeric antigen receptorNon-specific actionT cell linesHuman T cellsDominant cell typeHuman insulitisPathogenic subpopulationsNovel immunotherapiesPrimary human T cellsClinical trialsPrimary mediatorPeptide epitopesAntigen receptorMicroglobulin complexCAR signaling
2015
A Preclinical Consortium Approach for Assessing the Efficacy of Combined Anti-CD3 Plus IL-1 Blockade in Reversing New-Onset Autoimmune Diabetes in NOD Mice
Gill RG, Pagni PP, Kupfer T, Wasserfall CH, Deng S, Posgai A, Manenkova Y, Hani A, Straub L, Bernstein P, Atkinson MA, Herold KC, von Herrath M, Staeva T, Ehlers MR, Nepom GT. A Preclinical Consortium Approach for Assessing the Efficacy of Combined Anti-CD3 Plus IL-1 Blockade in Reversing New-Onset Autoimmune Diabetes in NOD Mice. Diabetes 2015, 65: 1310-1316. PMID: 26718498, PMCID: PMC5860426, DOI: 10.2337/db15-0492.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAutoimmune DiseasesBiomedical ResearchCD3 ComplexDiabetes Mellitus, Type 1Drug Administration ScheduleDrug Therapy, CombinationFemaleImmunoglobulin Fab FragmentsImmunotherapyInsulinInsulin SecretionInsulin-Secreting CellsInterleukin-1 Receptor Accessory ProteinInterleukin-1betaMice, Inbred NODMulticenter Studies as TopicPilot ProjectsReceptors, Interleukin-1 Type IRecombinant Fusion ProteinsReproducibility of ResultsResearch DesignSpecific Pathogen-Free OrganismsUnited StatesConceptsNew-onset diseaseIL-1 blockadeAnti-CD3 treatmentNOD micePreclinical studiesInterleukin-1IL-1β monoclonal antibodyIslet β-cell massNOD mouse modelImmune Tolerance NetworkType 1 diabetesΒ-cell massApplicable immunotherapiesFuture clinical useStudy entryProspective studyClinical trialsMouse modelMulticenter consortiumAnimal modelsCandidate therapeuticsClinical useTherapeutic agentsMonoclonal antibodiesDisease
2013
Immune Therapy and β-Cell Death in Type 1 Diabetes
Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, Gottlieb P, Akirav EM, Bluestone JA, Herold KC. Immune Therapy and β-Cell Death in Type 1 Diabetes. Diabetes 2013, 62: 1676-1680. PMID: 23423576, PMCID: PMC3636605, DOI: 10.2337/db12-1207.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, Monoclonal, HumanizedC-PeptideCD3 ComplexCytotoxicity Tests, ImmunologicCytotoxicity, ImmunologicDiabetes Mellitus, Type 1DNA MethylationFemaleHumansHypoglycemic AgentsImmunologic FactorsImmunotherapyInsulinInsulin SecretionInsulin-Secreting CellsIslets of LangerhansMalePostprandial PeriodYoung AdultConceptsRecent-onset T1DΒ-cell deathΒ-cellsNondiabetic subjectsImmune therapyType 1 diabetes resultsAnti-CD3 monoclonal antibodyUnmethylated INS DNAC-peptide responseNondiabetic control subjectsΒ-cell functionInsulin-producing β-cellsHigh rateImmune interventionDiabetes resultsControl subjectsClinical trialsPatientsT1DType 1Monoclonal antibodiesDeathTeplizumabINS DNATherapy
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