Biomaterials-based metabolic rescue of dendritic cells for vaccine design
基于生物材料的树突状细胞代谢拯救用于疫苗设计
基本信息
- 批准号:10543178
- 负责人:
- 金额:$ 32.28万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdjuvantAdoptive TransferAntigen-Presenting CellsAntigensBRAF geneBiocompatible MaterialsBiological AssayBone MarrowCD8-Positive T-LymphocytesCD8B1 geneCancer VaccinesCarbonCellsCitric Acid CycleCollecting CellCombination immunotherapyComplexContralateralCytotoxic T-LymphocytesDataDendritic CellsDendritic cell activationDevelopmentDopachrome isomeraseDoseFormulationFrequenciesFructoseFutureGATA3 geneGenerationsGenus HippocampusGlutaminaseGlycolysisGlycolysis InhibitionGlycolysis PathwayGoalsGrowthHelper-Inducer T-LymphocyteHumanImmuneImmunocompetentImmunohistochemistryImmunotherapyIn VitroIntravenousKidneyKineticsLiverLysineMacrophageMalignant NeoplasmsMalignant neoplasm of ovaryMaximum Tolerated DoseMeasuresMetabolicMetabolic PathwayMetabolismMissionMitochondriaModelingMusNF-kappa BOrganOxygen ConsumptionPathway interactionsPeptidesPhagocytosisPoly I-CPolymersProductionProliferatingPublic HealthPublishingReactionReactive Oxygen SpeciesResearchResearch Project GrantsRespirationRoleSafetySortingStress TestsSuccinatesT cell responseT memory cellT-LymphocyteTechnologyTestingToxic effectTreatment ProtocolsTumor BurdenTumor-Infiltrating LymphocytesTumor-infiltrating immune cellsUnited States National Institutes of HealthVaccine DesignVaccine TherapyVaccinesVertebral columnWorkappropriate dosecancer cellcancer typecytotoxicdraining lymph nodeethylene glycolexhaustexperimental studyextracellularin vivoinhibitorinorganic phosphatelong term memorylymph nodesmelanomametabolic fitnessmitochondrial fitnessmouse modelmutantnanoparticleneoplasm immunotherapynovelparticlepreventprogrammed cell death protein 1programsresponsescale upsubcutaneoustumortumor growthtumor microenvironmentvaccine efficacyvaccine response
项目摘要
Abstract
The main goal of this proposal is to develop biomaterial-based technologies that can modulate the functions of
DCs and T-cells in the draining lymph nodes in the presence of systemically delivered metabolic inhibitors. The
hypothesis of this proposal is that polymeric biomaterials-based particles generated from central-carbon
metabolites (targeting DCs via phagocytosis) can restart glycolysis/TCA cycle in DCs in the presence of
metabolic inhibitors and will also induce robust vaccine responses in immunocompetent mice. Notably, we
have generated polymers of central-carbon metabolites from glycolysis and TCA cycle, which were able to
activate DCs even in the presence of metabolic inhibitors. Moreover, these particles were able to rescue the
metabolic inhibition, as observed by up-regulated extracellular acidification rate (ECAR) and oxygen
consumption rate (OCR) in bone marrow derived DCs. In vivo PEGS particle formulations delivering TRP-2
peptide (without any adjuvant), were able to prevent the growth of subcutaneous B16F10 tumors in the
presence of CB-839 a glutaminase inhibitor. Similarly, F16BP vaccine particles delivering TRP2 peptide
antigen along with poly(I:C) as adjuvant and PFK15, a glycolytic inhibitor, were able to reverse the growth of
subcutaneous YUMM1.1 tumors. The hypothesis of this proposal will be tested using the following specific
aims: Aim 1: Evaluate if F16BP particles induce antigen-specific long-term memory T cell responses in
immunocompetent mice in the presence of glycolytic inhibitor PFK15. Aim 2: Determine if PEGS particles can
induce antigen-specific long-term T cell responses in immunocompetent mice in the presence of glutaminase
inhibitor CB-839. Aim 3: Determine toxicity profile and maximum tolerable doses of vaccines. The results
obtained from these experiments will shed light on the effect of metabolic reprogramming on the efficacy of
vaccine therapy.
摘要
项目成果
期刊论文数量(0)
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Abhinav Acharya其他文献
Abhinav Acharya的其他文献
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{{ truncateString('Abhinav Acharya', 18)}}的其他基金
Local immunometabolism modulating biomaterials for immunosuppressive applications
用于免疫抑制应用的局部免疫代谢调节生物材料
- 批准号:
10405419 - 财政年份:2021
- 资助金额:
$ 32.28万 - 项目类别:
Biomaterials-based metabolic rescue of dendritic cells for vaccine design
基于生物材料的树突状细胞代谢拯救用于疫苗设计
- 批准号:
10322658 - 财政年份:2021
- 资助金额:
$ 32.28万 - 项目类别:
Local immunometabolism modulating biomaterials for immunosuppressive applications
用于免疫抑制应用的局部免疫代谢调节生物材料
- 批准号:
10598113 - 财政年份:2021
- 资助金额:
$ 32.28万 - 项目类别:
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