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.

项目概要/摘要 外周 T 细胞淋巴瘤 (PTCL) 是一种异质性癌症，占所有非霍奇金癌症的 20% 淋巴瘤 (NHL) 世界卫生组织分类承认许多不同的亚型。 但即使对于血液病理学家来说，这些不同亚型的诊断也具有挑战性。 此外，使用当前的方法，30-50% 的 PTCL 病例根本无法分类为任何特定亚型。 根据目前的护理标准，PTCL 患者的预后通常较差。 过去二十年来，PTCL 患者的治疗效果并未取得任何改善。 然而，针对特定 PTCL 亚型的新疗法最近已开始测试，其中一些疗法具有 因此，准确诊断 PTCL 及其亚型已变得至关重要。 该项目将为每位患者选择最合适、最有效的治疗方法。 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 分子谱分析项目 (LLMPP)，其中稳健的分子基因表达 (GE) 特征已被 该项目将建立在这项工作的基础上，并将其用作 PTCL 的每个主要亚型所特有的。 为常规临床应用创建商业化验以改善诊断奠定基础， HealthChart LLC 是一家最近成立的分子诊断公司。 专注于开发针对癌症和其他疾病的利基适应症的新型诊断测定法， 已获得与学术工作相关的知识产权和专利组合的许可，并且是 这些拟议研究中的小型企业合作伙伴 第一阶段 STTR 提案的总体目标。 的目的是转变最初使用开发的“学术”PTCL 诊断和预后 GE 特征 使用表达微阵列分析新鲜冷冻样本以获得优化的锁定特征 适用于在 NanoString nCounter 上分析的福尔马林固定石蜡包埋 (FFPE) 标本 该提案的两个目标 - 目标 1. 确定一组精简的转录本并创建一个新颖的版本。 模型能够复制现有的“学术”诊断和预后 PTCL 特征；目标 2。 确认精细诊断和预后 PTCL 基因特征集在 用于分析 FFPE 样本的 nCounter 平台 (NanoString) – 将创建一个优化且 锁定 PTCL 签名，建立实验室间再现性的性能规范，并验证 这些研究将使该测定法能够作为 CLIA 进行应用。 在第一阶段结束时提供实验室服务，同时将 PTCL 检测定位为过渡到第二阶段开发 用于新型和/或现有 PTCL 的体外诊断 (IVD) 套件以及可能的伴随诊断 (CDx) 疗法。