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.
Public Health Relevance Statement: Project Narrative Peripheral T-cell lymphomas (PTCL) are a heterogeneous, difficult-to-diagnose group of cancers that constitute up to 20% of all non-Hodgkin lymphomas (NHL) and are associated with a poor prognosis, with no improvement in outcomes over the past two decades. However, novel therapies targeted to specific subtypes of PTCL have recently begun to undergo testing, some with spectacular results. This scientific proposal describes the development of a novel clinical diagnostic test for commercial application that is designed to reliably identify the subtypes of PTCL, thus helping to ensure the selection of the most appropriate and effective treatments for each individual patient and ultimately improving the outcomes of individuals with these cancers.
Project Terms: accurate diagnosis; Agreement; Algorithms; assay development; base; Biological Assay; Businesses; Cell Line; Cities; Classification; CLIA certified; clinical application; clinical diagnostics; clinical subtypes; clinically relevant; cohort; commercial application; companion diagnostics; Consult; Data; design; Detection; Development; Diagnosis; Diagnostic; diagnostic assay; Diagnostic Procedure; Diagnostic tests; Disease; effective therapy; Elements; Ensure; Formalin; Freezing; Gene Chips; Gene Expression Profile; Gene Expression Profiling; Genes; genetic signature; Goals; Gold; Human; improved; improved outcome; In Vitro; Individual; individual patient; insight; Intellectual Property; Laboratories; Laboratory Study; Legal patent; leukemia/lymphoma; Lymphoid Cell; Lymphoid Tissue; Lymphoma; Malignant Neoplasms; Modeling; Molecular; molecular diagnostics; Molecular Profiling; nano-string; new therapeutic target; Non-Hodgkin's Lymphoma; novel; novel diagnostics; Outcome; outcome forecast; Paraffin Embedding; Patients; Performance; Peripheral; Phase; phase 1 study; Positioning Attribute; prognostic; prognostic signature; Reagent; Reproducibility; Research Personnel; RNA; Running; Sampling; Seminal; Sensitivity and Specificity; Site; Small Business Technology Transfer Research; Specimen; standard of care; T-Cell Lymphoma; Testing; Tissue Embedding; Training; Transcript; Treatment outcome; Validation; Work; World Health Organization
