Validation of CD6 as a New Target for Treating Multiple Sclerosis
验证 CD6 作为治疗多发性硬化症的新靶点
基本信息
- 批准号:8700553
- 负责人:
- 金额:$ 19.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-08-01 至 2016-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAnimal ModelAnimalsAntibodiesAutoimmune DiseasesBiological Response Modifier TherapyCD6 antigenChimeric ProteinsChronicClinicalDataDevelopmentDiseaseDisease ProgressionEffectivenessEngineered GeneExperimental Autoimmune EncephalomyelitisFutureGenome ScanHumanImmunoglobulin GIn VitroKnockout MiceLeadMembrane GlycoproteinsModelingMultiple SclerosisMusPatientsPilot ProjectsProteinsRattusReagentRecurrent diseaseRelapseRelative (related person)ResearchStagingT cell responseT-LymphocyteTestingTherapeutic AgentsTreatment EfficacyValidationWild Type Mousecentral nervous system injuryefficacy testingin vivonovelnovel strategiesnovel therapeuticspreventpublic health relevancerisk varianttherapeutic targettool
项目摘要
DESCRIPTION (provided by applicant): CD6 is a cell surface glycoprotein that is primarily expressed on T cells. Previous in vitro studies have indicated that CD6 is critical in regulating T
cell responses and that it could be a target for treating autoimmune diseases. However, research in this field has languished, partially due to the lack of CD6 gene engineered animals to confirm the in vitro results and to explore the potential of biologic therapy in vivo. Recent genome scanning studies from several groups have unanimously identified CD6 as a risk gene for multiple sclerosis (MS), which raises the possibility of using CD6 as a target to develop new therapies for MS. We have studied CD6 knockout (KO) mice and discovered that they are protected from central nervous system injury in experimental autoimmune encephalomyelitis (EAE), an animal model of human MS, further supporting the hypothesis that targeting CD6 could be effective in treating MS. To test this hypothesis, we treated wild type (WT) mice after onset of EAE with a rat anti-mouse CD6 mAb and found that this halted disease progression, but the efficacy of treatment rapidly decreased due to the development of anti-rat IgG antibodies in the treated mice. To address this issue and to be able to test human CD6-targeted reagents in vivo, we have developed CD6 humanized mice that express human CD6 instead of mouse CD6 on their T cells. In pilot treatment studies using these CD6 humanized mice, we found that administration of a mouse anti-human CD6 mAb (UMCD6) at either an early stage (clinical score H1) or late stage (clinical score H2.5) of EAE significantly reversed disease progression and this effect was long-lasting. In this application, using the CD6 humanized mice, we will further test this mAb and another well-characterized mouse anti-human CD6 mAb and a soluble human CD6-Fc chimeric protein to determine their relative effectiveness in treating both chronic progressive EAE, and remitting-relapsing EAE. This study should validate CD6 as a new target for MS therapy and set the stage for further development of the anti-CD6 mAbs and soluble CD6-Fc protein as novel therapeutic agents for MS patients.
描述(由申请人提供):CD6是一种主要在T细胞上表达的细胞表面糖蛋白。先前的体外研究表明,CD6在调节T中起关键作用
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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FENG C LIN其他文献
FENG C LIN的其他文献
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{{ truncateString('FENG C LIN', 18)}}的其他基金
Role of CDCP1 in the pathogenesis of autoimmune uveitis
CDCP1在自身免疫性葡萄膜炎发病机制中的作用
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Development of a novel antibody-drug conjugate for treating T-cell lymphoma.
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10545523 - 财政年份:2022
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Development of a new drug for treating autoimmune uveitis
治疗自身免疫性葡萄膜炎新药的研制
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10321980 - 财政年份:2021
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$ 19.61万 - 项目类别:
New mechanisms by which complementýregulates the pathogenesis of experimental autoimmune uveitis
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10175270 - 财政年份:2021
- 资助金额:
$ 19.61万 - 项目类别:
New mechanisms by which complementýregulates the pathogenesis of experimental autoimmune uveitis
补体调节实验性自身免疫性葡萄膜炎发病机制的新机制
- 批准号:
10397686 - 财政年份:2021
- 资助金额:
$ 19.61万 - 项目类别:
New mechanisms by which complementýregulates the pathogenesis of experimental autoimmune uveitis
补体调节实验性自身免疫性葡萄膜炎发病机制的新机制
- 批准号:
10619536 - 财政年份:2021
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$ 19.61万 - 项目类别:
A novel regulator of Pseudomonas aeruginosa keratitis
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10618396 - 财政年份:2020
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$ 19.61万 - 项目类别:
A novel regulator of Pseudomonas aeruginosa keratitis
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10401830 - 财政年份:2020
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$ 19.61万 - 项目类别:
A novel regulator of corneal wound healing and Pseudomonas aeruginosa keratitis
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9898378 - 财政年份:2019
- 资助金额:
$ 19.61万 - 项目类别:
A novel regulator of corneal wound healing and Pseudomonas aeruginosa keratitis
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- 批准号:
10391450 - 财政年份:2019
- 资助金额:
$ 19.61万 - 项目类别:
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