Development of a Novel Clinical Diagnostic Assay for Peripheral T-cell Lymphoma (PTCL)

开发外周 T 细胞淋巴瘤 (PTCL) 的新型临床诊断方法

• 批准号: 9555564
• 负责人: Wing C. Chan
• 金额: $ 29.94万
• 依托单位: HEALTHCHART, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9555564
• 关键词: Agreement; Algorithms; Biological Assay; Businesses; CLIA certified; Cell Line; Cities; Classification; Consult; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Elements; Ensure; Formalin; Freezing; Gene Chips; Gene Expression Profile; Gene Expression Profiling; Genes; Goals; Gold; Human; In Vitro; Individual; Intellectual Property; Laboratories; Laboratory Study; Legal patent; Lymphoid Cell; Lymphoid Tissue; Lymphoma; Malignant Neoplasms; Modeling; Molecular; Molecular Profiling; Non-Hodgkin' s Lymphoma; Outcome; Paraffin Embedding; Patients; Performance; Peripheral; Phase; Positioning Attribute; RNA; Reagent; Reproducibility; Research Personnel; Running; Sampling; Seminal; Sensitivity and Specificity; Site; Small Business Technology Transfer Research; Specimen; T-Cell Lymphoma; Testing; Tissue Embedding; Training; Transcript; Treatment outcome; Validation; Work; World Health Organization; accurate diagnosis; assay development; base; clinical application; clinical diagnostics; clinical subtypes; clinically relevant; cohort; commercial application; companion diagnostics; design; diagnostic assay; effective therapy; genetic signature; improved; improved outcome; individual patient; insight; leukemia/lymphoma; molecular diagnostics; nano-string; new therapeutic target; novel; novel diagnostics; outcome forecast; phase 1 study; prognostic; prognostic signature; standard of care; Agreement; Algorithms; Biological Assay; Businesses; CLIA certified; Cell Line; Cities; Classification; Consult; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Elements; Ensure; Formalin; Freezing; Gene Chips; Gene Expression Profile; Gene Expression Profiling; Genes; Goals; Gold; Human; In Vitro; Individual; Intellectual Property; Laboratories; Laboratory Study; Legal patent; Lymphoid Cell; Lymphoid Tissue; Lymphoma; Malignant Neoplasms; Modeling; Molecular; Molecular Profiling; Non-Hodgkin' s Lymphoma; Outcome; Paraffin Embedding; Patients; Performance; Peripheral; Phase; Positioning Attribute; RNA; Reagent; Reproducibility; Research Personnel; Running; Sampling; Seminal; Sensitivity and Specificity; Site; Small Business Technology Transfer Research; Specimen; T-Cell Lymphoma; Testing; Tissue Embedding; Training; Transcript; Treatment outcome; Validation; Work; World Health Organization; accurate diagnosis; assay development; base; clinical application; clinical diagnostics; clinical subtypes; clinically relevant; cohort; commercial application; companion diagnostics; design; diagnostic assay; effective therapy; genetic signature; improved; improved outcome; individual patient; insight; leukemia/lymphoma; molecular diagnostics; nano-string; new therapeutic target; novel; novel diagnostics; outcome forecast; phase 1 study; prognostic; prognostic signature; standard of care

Project Summary/Abstract Peripheral T-cell lymphoma (PTCL) is a heterogeneous cancer that constitutes up to 20% of all non-Hodgkin lymphoma (NHL). The World Health Organization classification recognizes a number of distinct subtypes of PTCL but the diagnosis of these different subtypes is challenging even for expert hematopathologists. Furthermore, 30-50% of PTCL cases are not classifiable into any specific subtype at all using current diagnostic methods. Patients with PTCL generally have a poor prognosis with current standard-of-care therapy, and no improvement in the outcome of PTCL patients has been achieved in the last two decades. However, novel therapies targeted to specific PTCL subtypes have recently begun testing, some with spectacular results. Accurate diagnosis of PTCL and its subtypes has therefore become essential to ensure selection of the most appropriate and effective treatment for each individual patient. This project will leverage seminal work performed by academic investigators associated with the Lymphoma/Leukemia Molecular Profiling Project (LLMPP), in which robust molecular gene expression (GE) signatures have been identified that are unique to each major subtype of PTCL. The project will build upon this work, utilizing it as the basis for the creation of a commercial assay for routine clinical application to improve the diagnosis, treatment, and outcomes of PTCL patients. HealthChart LLC, a recently founded molecular diagnostics firm focused on the development of novel diagnostic assays for niche indications in cancer and other diseases, has licensed the intellectual property and patent portfolio associated with the academic work and is the small business partner in these proposed studies. The overarching goal of this Phase 1 STTR proposal is to transition the “academic” PTCL diagnostic and prognostic GE signatures originally developed using fresh frozen specimens analyzed with expression microarrays to an optimized, locked-down signature applicable to formalin-fixed paraffin-embedded (FFPE) specimens analyzed on the NanoString nCounter platform. The two Aims of this proposal – Aim 1. Identify a reduced set of transcripts and create a novel model able to replicate the existing “academic” diagnostic and prognostic PTCL signature; Aim 2. Confirm the applicability of the refined diagnostic and prognostic PTCL gene signature sets on the nCounter platform (NanoString) for the analysis of FFPE specimens – will create an optimized and locked-down PTCL signature, establish performance specifications for inter-lab reproducibility, and validate the signature to a rigorous set of target metrics. These studies will enable application of the assay as a CLIA lab offering at the end of Phase 1, while positioning the PTCL assay for transition to Phase 2 development as an in vitro diagnostic (IVD) kit and possibly a companion diagnostic (CDx) for novel and/or existing PTCL therapies.

项目摘要/摘要 周围T细胞淋巴瘤（PTCL）是一种异质性癌症，占所有非霍奇金的20％ 淋巴瘤（NHL）。世界卫生组织分类认识到许多不同的亚型 PTCL，但这些不同亚型的诊断即使对于专家血管病理学家来说也是有挑战性的。 此外，使用电流完全不可用30-50％ 诊断方法。 PTCL患者的预后较差，当前护理标准 在过去的二十年中，PTCL患者的预后没有改善，并且没有改善。 然而，针对特定PTCL亚型的新型疗法最近开始进行测试，有些则是 壮观的结果。因此，PTCL及其亚型的准确诊断对于确保 为每个患者选择最合适，最有效的治疗方法。这个项目将 利用与淋巴瘤/白血病相关的学术研究人员进行的第二次工作 分子分析项目（LLMPP），其中强大的分子基因表达（GE）签名已 鉴定出PTCL的每个主要亚型独有的。该项目将以这项工作为基础 创建商业评估的常规临床应用以改善诊断的基础， PTCL患者的治疗和结果。 HealthChart LLC，最近创立的分子诊断公司 专注于开发癌症和其他疾病的小众适应症的新型诊断测定法 已许可与学术工作相关的知识产权和专利组合 这些提议的研究中的小企业合作伙伴。此阶段1 STTR提案的总体目标 是过渡最初使用的“学术” PTCL诊断和预后的GE签名 用表达微阵列分析的新鲜冷冻标本，以优化，锁定的签名 适用于在纳米弦ncounter上分析的福尔马林固定石蜡包裹（FFPE）标本 平台。该提案的两个目标 - 目标1。确定减少的成绩单并创建小说 模型可以复制现有的“学术”诊断和预后的PTCL签名；目标2。 确认精制诊断和预后的PTCL基因签名集的适用性 用于分析FFPE标本的NCounter平台（纳米弦） - 将创建优化和 锁定的PTCL签名，建立LAB间可重复性的性能规格并验证 签名到严格的目标指标。这些研究将使该测定法应用于CLIA 在第1阶段结束时提供实验室产品，同时将PTCL分析定位为过渡到第2阶段开发 体外诊断（IVD）套件，并可能用于新颖和/或现有PTCL的伴侣诊断（CDX） 疗法。