Nanoimmunotherapy for chronic immune-mediated diseases
纳米免疫疗法治疗慢性免疫介导疾病
基本信息
- 批准号:10483819
- 负责人:
- 金额:$ 30万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-14 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAlpha Interleukin 2 ReceptorAmericanAnimal ModelAnti-Inflammatory AgentsAntibodiesAntigen-Presenting CellsAntigensArtificial nanoparticlesAttentionAutoantibodiesAutoantigensAutoimmuneAutoimmune DiseasesAutoimmunityB-LymphocytesBiological AssayCD3 AntigensCD8B1 geneCellsChimeric ProteinsChronicClinicalClinical TrialsDiseaseDisease OutcomeDisease ProgressionDisease remissionDrug usageEncapsulatedEngineeringEnvironmentExperimental Autoimmune EncephalomyelitisFOXP3 geneFlow CytometryFormulationGenerationsGoalsGrantHomeostasisHost DefenseHumanHyperactivityImmuneImmune ToleranceImmune responseImmune systemImmunosuppressive AgentsImpairmentIn VitroIndividualInflammationInflammatoryInsulin-Dependent Diabetes MellitusInterleukin-2LearningLupusLymphocyteLymphocyte FunctionMediatingMethodologyMultiple SclerosisMusNanoimmunotherapyNatural Killer CellsPathogenicityPeptidesPeripheral Blood Mononuclear CellPharmacologic SubstancePhasePhenotypePlayPopulationPrevalenceProcessProductionPropertyPublic HealthPublishingRecombinantsRegulatory T-LymphocyteRoleSafetySuppressor-Effector T-LymphocytesSystemic Lupus ErythematosusT-LymphocyteTherapeuticTherapeutic AgentsTimeTissuesToxic effectTransforming Growth Factor betaUnited States National Institutes of HealthWorkautoreactive T cellcomparative efficacycostcost effectivecytokinedesigndisabilityeffector T cellexperimental studygraft vs host diseasehuman modelhumanized mouseimmunoregulationimprovedin vitro activityin vivolupus-likemortalitynanoparticlenovelnovel strategiesphase 1 studypreventresponsescale upside effectvirtual
项目摘要
ABSTRACT
Current pharmaceutical agents that are used for the treatment of immune-mediated inflammatory
conditions including autoimmune diseases generally do not lead to remission and frequently carry toxic
side effects. Here we propose a strategy that can harness the capacity of the immune system to induce
immunoregulatory response that can suppress immune hyperactivity and chronic inflammation in vivo.
The product that we propose consists of nanoparticles (NPs) targeted to immunoregulatory cells for
their expansion and functional activity in vitro and in vivo. Our approach to generate and expand
functional immunoregulatory cells that become impaired in autoimmune diseases should contribute to
restoring immune homeostasis and improve disease outcomes. This approach is especially designed
to treat systemic lupus erythematosus. The proof-of-concept for this Phase 1 studies will be to show
that our cell-targeted NPs can markedly expand ex vivo both CD4+ and CD8+ Tregs, and TGF-ß
producing NK regulatory cells that we recently described. Complementary experiments in humanized
mice will address the in vivo functional efficacy of those NP-induced immunoregulatory cells in
suppressing effector immune responses in vivo, including in an animal model of human lupus. By
demonstrating that NP-expanded human immunoregulatory cells are functional in vivo in humanized
mice, we propose a new nanoimmunotherapeutic approach to restore immune regulation and induce
remission in autoimmune disease. Importantly, this in vivo cell-targeted strategy has the potential to
overcome the undesired side effects of the broadly non-specific, anti-inflammatory and
immunosuppressive drugs presently used to treat autoimmune diseases.
摘要
目前用于治疗免疫介导的炎性疾病的药剂
包括自身免疫性疾病在内的病症通常不会导致缓解,
副作用.在这里,我们提出了一种策略,可以利用免疫系统的能力,
免疫调节反应,可以抑制体内免疫过度活跃和慢性炎症。
我们提出的产品由靶向免疫调节细胞的纳米颗粒(NPs)组成,
它们在体外和体内的扩增和功能活性。我们的方法来生成和扩展
在自身免疫性疾病中受损的功能性免疫调节细胞应该有助于
恢复免疫稳态并改善疾病结果。这种方法是特别设计的,
治疗系统性红斑狼疮。本1期研究的概念验证将显示
我们的细胞靶向纳米颗粒可以显着扩增离体的CD 4+和CD 8 + T细胞,和TGF-β
产生我们最近描述的NK调节细胞。人源化的补充实验
小鼠将解决这些NP诱导的免疫调节细胞在体内的功能功效,
抑制体内效应免疫应答,包括在人狼疮的动物模型中。通过
这证明NP扩增的人免疫调节细胞在人源化免疫调节细胞中体内是有功能的。
小鼠,我们提出了一种新的纳米免疫方法来恢复免疫调节,
自身免疫性疾病的缓解。重要的是,这种体内细胞靶向策略有可能
克服广泛非特异性、抗炎和抗病毒药物的不良副作用
目前用于治疗自身免疫性疾病的免疫抑制药物。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Low-dose interleukin-2 therapy in systemic lupus erythematosus.
- DOI:10.2478/rir-2023-0021
- 发表时间:2023-09
- 期刊:
- 影响因子:0
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{{ truncateString('DAVID A HORWITZ', 18)}}的其他基金
IMMUNOREGULATORY MECHANISMS IN THE RHEUMATIC DISEASES
风湿性疾病的免疫调节机制
- 批准号:
2882234 - 财政年份:1980
- 资助金额:
$ 30万 - 项目类别: