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New approach for immune modulation against T1D

New approach for immune modulation against T1D
针对 T1D 免疫调节的新方法
批准号:
10699223
负责人:
Weston Daniel
金额:
$76.18万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-09-20 至 2025-08-31
关键词:
AcuteAddressAdjuvantAffectAgeAntigen PresentationAntigen-Presenting CellsAntigensApolipoprotein A-IAutoantigensAutoimmune DiseasesAutoimmunityBeta CellBiological AssayBystander SuppressionCD8-Positive T-LymphocytesCell physiologyClinical ChemistryClinical ProtocolsDataDendritic CellsDiseaseDisease susceptibilityDoseDrug KineticsEpitopesEvaluationExperimental Autoimmune EncephalomyelitisFeedbackFormulationFutureGoalsHigh Density LipoproteinsHumanHyperglycemiaIL17 geneIgG autoantibodiesImmune ToleranceImmune mediated destructionImmune responseImmunityImmunologicsImmunotherapyImpairmentIn VitroInflammatoryInsulinInsulin Infusion SystemsInsulin-Dependent Diabetes MellitusInterferon Type IIKnowledgeLaboratoriesLinkLymphModelingMononuclearMusOrganOutcomePancreasPathogenicityPathologyPathway interactionsPatientsPeripheral Blood Mononuclear CellPersonsPhagocytosisPhasePhospholipidsProcessPublic HealthRattusRegimenRegulatory T-LymphocyteReportingResearchSafetySystemT cell responseT-LymphocyteTherapeuticToxicologyTreatment EfficacyVaccinesanalytical methodautoreactive T cellautoreactivitycancer vaccinationclinical developmentclinical translationcytokinedrug developmenteffective therapygood laboratory practiceimmunological interventionimmunomodulatory strategyimmunoregulationlead candidatelymph nodesmanufacturemanufacturing processmeetingsmouse modelnanodisknanoparticlenovel strategiespeptidomimeticspre-Investigational New Drug meetingpreventprocess optimizationprogrammed cell death ligand 1restraintstandard of caretumortumor-immune system interactions

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英文摘要
PROJECT SUMMARY/ABSTRACT Type 1 diabetes (T1D) is an autoimmune disease that affects 1 in 300 people by the age of 18 in the US. T1D is characterized by acute onset of hyperglycemia resulting from immune-mediated destruction of the insulin- producing β-cells in the pancreas. There is currently no cure for T1D and the disease requires constant management where the current standard of care/management is injected or pumped insulin. Thus, there is an urgent need for new and effective treatment options for T1D patients. While self-reactive CD4 and CD8 T cells are central pathogenic drivers, regulatory T cells (Tregs) have been shown to restrain autoimmunity and maintain immune tolerance through multiple mechanisms. In T1D patients, impaired Treg function have been shown to contribute to disease susceptibility. Thus, induction of Tregs holds great promise in correcting the aberrant autoreactive T cell activities and preventing the progression of T1D. However, it remains unknown how to induce Tregs in a safe and effective manner for the potential treatment of T1D. Here, we propose to develop a novel strategy for immunotherapy against T1D. Toward this goal, we have developed synthetic high-density lipoprotein NanoDiscs that are particularly well suited for lymph node targeting. Our preliminary data generated in a murine model of T1D and experimental autoimmune encephalomyelitis have shown that NanoDiscs carrying antigens only induce robust Treg response and achieve immune tolerance. Based on our compelling proof-of-concept data, we propose to develop NanoDiscs carrying antigens to promote antigen-specific immune tolerance against T1D. The proposed research will provide a new strategy for modulating immune microenvironment of pancreas and an avenue for immune tolerance against T1D.
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