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.

项目总结/文摘