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Machine learning optimized autoimmune therapeutics with a focus on Type 1 Diabetes

Machine learning optimized autoimmune therapeutics with a focus on Type 1 Diabetes
机器学习优化自身免疫疗法，重点关注 1 型糖尿病
批准号：
10697204
负责人：
David K Gifford
金额：
$30.65万
依托单位：
THINK THERAPEUTICS, INC.
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：
2023-09-15 至 2025-08-31
来源：
https://reporter.nih.gov/project-details/10697204
关键词：
Admission activityAllelesAmino Acid SequenceAntigensAutoantigensAutoimmuneAutoimmune DiseasesAutoimmunityBiological AssayBusinessesCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCD8B1 geneCell physiologyCell surfaceCellsCodeCollaborationsComputing MethodologiesCytotoxic T-LymphocytesDataDatabasesDerivation procedureDiabetes MellitusEpitopesFOXP3 geneFoundationsFrequenciesHLA-A geneHaplotypesHumanImmuneImmune systemImmunologic SurveillanceIndividualInsulin-Dependent Diabetes MellitusKiller CellsLegal patentLettersLiteratureLymphocyteMHC Class I GenesMHC Class II GenesMachine LearningMass Spectrum AnalysisMassachusettsMessenger RNAMethodsNormal CellPeptide/MHC ComplexPeptidesPeripheral Blood Mononuclear CellPersonsPopulationProteinsRecoveryRegulatory T-LymphocyteResearchSamplingSignal TransductionSymptomsT-Cell ActivationT-Cell ReceptorT-LymphocyteT-cell receptor repertoireTestingTherapeuticUniversitiesVaccine DesignVaccinesWorkantigen testcross reactivitydesignhigh throughput screeningimmunogenicityimprovedmachine learning frameworkmachine learning methodmedical schoolsnovelpreproinsulinpreventreceptorreceptor bindingresponsevaccination outcomevaccine evaluation

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Project Summary We propose to develop a new immunogenicity assay and machine learning based framework for creating tolerization vaccines for autoimmune diseases with improved population coverage. In collaboration with Harvard University and the University of Massachusetts Chan Medical School Diabetes Center of Excellence we will develop a new assay, the Multiplexed Multi-antigen Activation Assay (MMAA), to discover self- antigens that are recognized by cytotoxic T cells in Type 1 Diabetes (T1D) (Aim 1). We will use the self-antigens we have confirmed to design novel multi-epitope tolerization vaccines and test the vaccines for their ability to expand CD4+ TReg cells in PBMCs from T1D donors (Aim 2). We will utilize new machine learning methods to modify and select vaccine epitopes to substantially improve tolerization vaccine population coverage. Our products will be the resulting vaccines.
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