Transforming the diagnosis and care of patients with CTCL using TCR sequencing
使用 TCR 测序改变 CTCL 患者的诊断和护理
基本信息
- 批准号:9904113
- 负责人:
- 金额:$ 67.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-04-23 至 2021-03-31
- 项目状态:已结题
- 来源:
- 关键词:BenignBiologicalBiotechnologyBloodCaringCellsClinicClinicalClinical TrialsClinical assessmentsClone CellsCollaborationsCollectionCountryCutaneous LymphomaCutaneous T-cell lymphomaDataDiagnosisDiagnostic testsDiseaseEarly DiagnosisEvaluationGoalsHigh-Throughput Nucleotide SequencingHospitalsImmuneIndividualIndustrializationInflammationInflammatoryLeadLiteratureMalignant - descriptorMalignant NeoplasmsMeasuresMethodologyMethodsMonitorNon-Hodgkin&aposs LymphomaPatient CarePatientsPhysiciansPrognostic MarkerReproducibilityResearchResourcesSamplingScientistServicesSkinSpecimenSymptomsT-Cell ReceptorT-LymphocyteT-cell diversityTechniquesTechnologyTestingTimeTranslational ResearchTreatment EfficacyWomanbaseclinical careclinical examinationdesignexperimental studyhigh riskimprovedindustry partnerinnovationlymph nodesmedical schoolsmultidisciplinarynext generationnovelnovel therapeuticsoutcome forecastprognostic assayspublic health relevanceresearch clinical testingresponseskin disorderskin lesiontooltranslational physiciantreatment responsetumor progression
项目摘要
DESCRIPTION (provided by applicant): There are three major clinical problems in treating cutaneous T-cell lymphomas (CTCL), non- Hodgkin's lymphomas characterized by inflammatory skin lesions. First, diagnosis of early-stage CTCL is difficult and takes on average six years, often delaying diagnosis until the disease becomes more aggressive. Second, 20% of early stage patients go on to progressive, often lethal disease and there is no validated way to identify
patients who will progress. Third, CTCL is both a skin lymphoma and inflammatory disease. Clinical assessment of skin inflammation doesn't necessarily reflect malignant T cell burden, making determination of responses to therapy difficult. We provide pilot data that high throughput TCR CDR3 sequencing (HTS) can diagnose CTCL even in its earliest stages by identifying and quantifying malignant clonal T cells in skin lesions. We show that it permits for the first time comprehensive studies of the malignant and benign T cell infiltrate in skin lesions that may lead to methods for identifying patients who will progress. Lastly, the ability of this technique to quantify malignant T cells makes it vastly superior to clinical examination as a way to assess responses to therapy. HTS is available as both a research and clinical test but is not currently used in CTCL clinics because its utility and reliability in CTCL have not been demonstrated. We have assembled a multi-institutional, multidisciplinary collaborative team of industrial scientists, physician scientist's expert in CTCL translational research and physician's expert in the care of CTCL patients. Our Industrial Partner, Adaptive Biotechnologies, is a pioneer in HTS technology. Our Academic Partner, Brigham and Women's Hospital at Harvard Medical School, is a world recognized center for CTCL translational research. We have forged a collaboration with three of the top CTCL Clinical Care Centers in the nation to identify and supply patient samples. In Aim 1, we propose experiments designed to demonstrate that evaluation of the malignant clone, combined with percentages of the top five benign clones, definitively diagnoses CTCL even in its earliest stages and discriminates it from benign inflammatory skin diseases. In Aim 2, we will evaluate immune based parameters predictive of progression in other cancers to determine if they can identify patients who will develop progressive CTCL. In Aim 3, we will utilize HTS in three separate clinical trials to definitively demonstrate its superiority to clinical examination in assessing responses to therapy. The goal of this proposal is to demonstrate that HTS can revolutionize the way CTCL is diagnosed and monitored, transforming the care of these patients and bringing HTS into common use as a diagnostic and prognostic test in CTCL clinics.
描述(申请人提供):皮肤T细胞淋巴瘤(CTCL)是以炎症性皮肤损害为特征的非霍奇金淋巴瘤,临床上存在三大问题。首先,早期CTCL的诊断很困难,平均需要六年时间,通常会推迟诊断,直到疾病变得更具侵袭性。其次,20%的早期患者发展为进行性疾病,通常是致命的,目前还没有有效的方法来识别
会进步的病人。第三,CTCL既是皮肤淋巴瘤又是炎症性疾病。对皮肤炎症的临床评估不一定反映恶性T细胞的负担,这使得确定对治疗的反应变得困难。我们提供的初步数据表明,高通量TCR CDR3测序(HTS)可以通过识别和量化皮肤病变中的恶性克隆性T细胞,甚至在CTCL的早期阶段就可以诊断CTCL。我们表明,它首次允许对皮肤病变中的恶性和良性T细胞渗透进行全面研究,这可能导致识别病情进展的患者的方法。最后,这项技术量化恶性T细胞的能力使其作为评估治疗反应的一种方法大大优于临床检查。HTS可以作为研究和临床试验,但目前还没有用于CTCL临床,因为它在CTCL中的有效性和可靠性尚未得到证明。我们已经组建了一支由工业科学家、CTCL翻译研究的内科科学家和CTCL患者护理方面的内科专家组成的多机构、多学科的协作团队。我们的工业合作伙伴自适应生物技术公司是HTS技术的先驱。我们的学术合作伙伴哈佛医学院布里格姆妇女医院是世界公认的CTCL翻译研究中心。我们已经与全国三家顶级的CTCL临床护理中心建立了合作关系,以识别和提供患者样本。在目标1中,我们提出的实验旨在证明,对恶性克隆的评估,结合前五名良性克隆的百分比,即使在CTCL的早期阶段就可以明确诊断,并将其与良性炎症性皮肤病区分开来。在目标2中,我们将评估预测其他癌症进展的基于免疫的参数,以确定它们是否可以识别将发展为进展性CTCL的患者。在目标3中,我们将在三个不同的临床试验中使用HTS,以明确证明它在评估治疗反应方面优于临床检查。这项提案的目的是证明HTS可以彻底改变CTCL的诊断和监测方式,改变这些患者的护理,并使HTS在CTCL诊所作为诊断和预后测试得到普遍使用。
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Progression of undiagnosed cutaneous lymphoma after anti-tumor necrosis factor-alpha therapy.
- DOI:10.1016/j.jaad.2017.12.068
- 发表时间:2018-06
- 期刊:
- 影响因子:13.8
- 作者:Martinez-Escala ME;Posligua AL;Wickless H;Rutherford A;Sable KA;Rubio-Gonzalez B;Zhou XA;Kaplan JB;Pro B;Choi J;Querfeld C;Rosen ST;Guitart J
- 通讯作者:Guitart J
Novel application of high-dose rate brachytherapy for severe, recalcitrant palmoplantar pustulosis.
高剂量率近距离放射治疗治疗严重顽固性掌跖脓疱病的新应用。
- DOI:10.1111/ced.12803
- 发表时间:2016
- 期刊:
- 影响因子:4.1
- 作者:Timerman,D;Devlin,PM;Nambudiri,VE;Wright,NA;Vleugels,RA;Clark,RA;Kupper,TS;Merola,JF;Patel,M
- 通讯作者:Patel,M
Topical Carmustine as Monotherapy or as Multimodality Therapy for Folliculotropic Mycosis Fungoides.
局部卡莫司汀作为单一疗法或多模式疗法治疗毛囊性蕈样肉芽肿。
- DOI:10.2340/00015555-2551
- 发表时间:2017
- 期刊:
- 影响因子:3.6
- 作者:MacArthur,KellyM;Jariwala,Neha;Kim,EllenJ;Rook,AlainH
- 通讯作者:Rook,AlainH
Multiple melanocytic nevi restricted to mycosis fungoides patches in pediatric and young-adult patients. The potential role of local immunosuppression.
儿童和年轻成人患者的多发性黑素细胞痣仅限于蕈样肉芽肿斑片。
- DOI:10.1111/pde.13738
- 发表时间:2019
- 期刊:
- 影响因子:1.5
- 作者:Martinez-Escala,MariaEstela;Amin,SapnaModi;Sable,KimberlyAnne;Gerami,Pedram;Guitart,Joan
- 通讯作者:Guitart,Joan
CD30+ Lymphoproliferative Disorders of the Skin.
CD30 皮肤淋巴增殖性疾病。
- DOI:10.1016/j.hoc.2016.11.006
- 发表时间:2017
- 期刊:
- 影响因子:0
- 作者:Sauder,MaxwellB;O'Malley,JohnT;LeBoeuf,NicoleR
- 通讯作者:LeBoeuf,NicoleR
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Rachael Ann Clark其他文献
Rachael Ann Clark的其他文献
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{{ truncateString('Rachael Ann Clark', 18)}}的其他基金
Skin Inflammation in Human Health and Disease, 2021
人类健康和疾病中的皮肤炎症,2021
- 批准号:
10222899 - 财政年份:2021
- 资助金额:
$ 67.34万 - 项目类别:
Generation of robust resident memory T cells in barrier tissues through skin vaccination
通过皮肤疫苗接种在屏障组织中生成强大的常驻记忆 T 细胞
- 批准号:
10408492 - 财政年份:2021
- 资助金额:
$ 67.34万 - 项目类别:
Optimizing pre-analytic sample handling for high throughput TCR sequencing in cutaneous T cell lymphoma
优化皮肤 T 细胞淋巴瘤高通量 TCR 测序的分析前样品处理
- 批准号:
10688079 - 财政年份:2020
- 资助金额:
$ 67.34万 - 项目类别:
Optimizing pre-analytic sample handling for high throughput TCR sequencing in cutaneous T cell lymphoma
优化皮肤 T 细胞淋巴瘤高通量 TCR 测序的分析前样品处理
- 批准号:
10814026 - 财政年份:2020
- 资助金额:
$ 67.34万 - 项目类别:
Optimizing pre-analytic sample handling for high throughput TCR sequencing in cutaneous T cell lymphoma
优化皮肤 T 细胞淋巴瘤高通量 TCR 测序的分析前样品处理
- 批准号:
10053369 - 财政年份:2020
- 资助金额:
$ 67.34万 - 项目类别:
Optimizing pre-analytic sample handling for high throughput TCR sequencing in cutaneous T cell lymphoma
优化皮肤 T 细胞淋巴瘤高通量 TCR 测序的分析前样品处理
- 批准号:
10247804 - 财政年份:2020
- 资助金额:
$ 67.34万 - 项目类别:
Using human skin grafted mice to identify biomarkers of exposure and study effects of radiation on skin
使用人类皮肤移植小鼠来识别暴露的生物标志物并研究辐射对皮肤的影响
- 批准号:
10551268 - 财政年份:2020
- 资助金额:
$ 67.34万 - 项目类别:
Optimizing pre-analytic sample handling for high throughput TCR sequencing in cutaneous T cell lymphoma
优化皮肤 T 细胞淋巴瘤高通量 TCR 测序的分析前样品处理
- 批准号:
10424577 - 财政年份:2020
- 资助金额:
$ 67.34万 - 项目类别:
Using human skin grafted mice to identify biomarkers of exposure and study effects of radiation on skin
使用人类皮肤移植小鼠来识别暴露的生物标志物并研究辐射对皮肤的影响
- 批准号:
10112825 - 财政年份:2020
- 资助金额:
$ 67.34万 - 项目类别:
Reversing immune evasion and enhancing immune detection with topical resiquimod
使用外用瑞西莫德逆转免疫逃避并增强免疫检测
- 批准号:
10241428 - 财政年份:2018
- 资助金额:
$ 67.34万 - 项目类别:
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