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Tissue-Anchored vs. Circulating Engineered Enzyme Constructs for Immunometabolic Resolution of Psoriasis

Tissue-Anchored vs. Circulating Engineered Enzyme Constructs for Immunometabolic Resolution of Psoriasis
组织锚定与循环工程酶构建体用于银屑病免疫代谢解决
批准号：
10667165
负责人：
Dorina Avram
金额：
$79.83万
依托单位：
UNIVERSITY OF FLORIDA
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：
2023-02-02 至 2028-01-31
来源：
https://reporter.nih.gov/project-details/10667165
关键词：
AddressAnti-Inflammatory AgentsAutoimmune DiseasesAutoimmune ResponsesBindingBiologicalCell physiologyCellsChimeric ProteinsChronicCirculationClinicalDataDiffusionDiseaseDoseEngineeringEnzymesEssential Amino AcidsGalectin 3GenesGlycosaminoglycansHalf-LifeHomeostasisIL17 geneImiquimodImmuneImmune responseImmunocompromised HostImmunofluorescence ImmunologicImmunosuppressionImmunotherapeutic agentImpairmentInfectionInflammationInflammatoryKynurenineLymphoid CellMaximum Tolerated DoseMetabolicMetabolismPathogenicityPathologyPatientsPharmaceutical PreparationsPlayPolysaccharidesPredispositionProductionPsoriasisResolutionRoleRouteSkinSterilityStimulusTherapeuticTissuesToxic effectTranslationsTryptophanTryptophan 2,3 DioxygenaseTryptophan Metabolism Pathwayautoinflammatoryautoinflammatory diseasesautosomal dominant mutationbeta-galactosidecarbohydrate binding proteincarbohydrate receptorcell typecytokineenzyme modelextracellularhuman modelimmune modulating agentsimmunoregulationin vivoinnovationinterleukin-17Einterleukin-22interleukin-23keratinocytemouse modelnovelnovel strategiesnovel therapeuticsprogramsresponserestorationside effectsuccesssystemic toxicityγδ T cells

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Project Summary/Abstract We have developed innovative new approaches of administering immunotherapeutic enzymes that robustly directs immune cells away from chronic inflammation toward homeostasis through metabolic programming. Innovative fusion protein enzyme constructs in both tissue-anchored and circulating forms are investigated, quantifying cellular mechanisms of action in order to determine if different administration routes offer advantages. There is considerable need for new therapeutic options for the chronic auto-inflammatory disease, psoriasis, which irreversibly damage epidermal tissues.
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