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

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 外周T细胞淋巴瘤(PTCL)是一种异质性肿瘤，占所有非霍奇金淋巴瘤的20% 淋巴瘤(NHL)。世界卫生组织的分类承认了许多不同的亚型 但这些不同亚型的诊断即使对专业的血液病理学家来说也是具有挑战性的。 此外，30%-50%的PTCL病例根本不能归类为任何特定的亚型 诊断方法。根据目前的护理标准，PTCL患者的预后一般较差。 在过去的二十年里，PTCL患者的预后没有任何改善。 然而，针对特定PTCL亚型的新疗法最近已开始测试，其中一些 令人惊叹的结果。因此，对PTCL及其亚型的准确诊断对于确保 为每个患者选择最合适和最有效的治疗方法。这个项目将 利用与淋巴瘤/白血病相关的学术研究人员所做的开创性工作 分子图谱计划(LLMPP)，在该计划中，强大的分子基因表达(GE)签名已经 确定了PTCL每个主要亚型所特有的基因。该项目将在这项工作的基础上，利用它作为 创建用于常规临床应用的商业分析以改进诊断的基础， PTCL患者的治疗和转归。HealthChart LLC，一家最近成立的分子诊断公司 重点开发癌症和其他疾病的利基适应症的新诊断分析方法， 已授权与学术工作相关的知识产权和专利组合，并是 这些拟议研究中的小企业合作伙伴。此第一阶段STTR提案的总体目标是 是将最初使用以下工具开发的“学术”PTCL诊断和预后GE信号 利用表达微阵列分析新鲜冷冻样品以获得优化、锁定的签名 适用于纳米串计数器分析的福尔马林固定石蜡包埋(FFPE)标本 站台。这项提议的两个目标-目标1.确定一组减少的成绩单并创作一部小说 能够复制现有的“学术”诊断和预后PTCL信号的模型；目标2。 确认改进的诊断和预后PTCL基因签名集在 用于分析FFPE样本的计数器平台(NanoString)-将创建一个优化的和 锁定PTCL签名，建立实验室间可重复性的性能规范，并验证 一套严格的目标指标的签名。这些研究将使该检测作为CLIA的应用成为可能 在第一阶段结束时提供实验室服务，同时将过渡到第二阶段开发的PTCL分析定位为 新的和/或现有的PTCL的体外诊断(IVD)试剂盒和可能的伴随诊断(CDX) 治疗。