RASL-Seq CTC Assay

RASL-Seq CTC 检测

基本信息

批准号：
8782292
负责人：
BRUCE E. SELIGMANN
金额：
$ 35万
依托单位：
BIOSPYDER TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-10 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8782292
关键词：
Antibodies Antigens Base Sequence Biological Assay Biological Markers Biopsy Cancer Patient Cell Count Cell Line Cell Separation Cell Therapy Cells Clinical Clinical assessments Companions Cytokeratin Detection Development Diagnostic Diagnostic tests Doctor of Medicine Drug Targeting Embryo Epithelial Evaluation FDA approved Gene Expression Gene Expression Profile Gene Expression Profiling Gene Targeting Genes Government Individual Legal patent Licensing Ligation Marketing Measurement Measures Mediating Mesenchymal Messenger RNA Methods Molecular Profiling Monitor Neoplasm Circulating Cells Neoplasm Metastasis Oncologist Outcome PTPRC gene Patient Care Patients Performance Persons Pharmaceutical Preparations Phase Population Predictive Value Progression-Free Survivals RNA Reagent Relapse Research Risk Sampling Sorting - Cell Movement TACSTD2 gene Technology Testing Therapeutic Agents Validation adduct base cancer cell cost established cell line genome sequencing improved innovation malignant breast neoplasm minimally invasive novel therapeutics prognostic programs public health relevance response success therapeutic target transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): This project will demonstrate the feasibility of identifying circulating tumor cells (CTCs) that have undergone an epithelial-mesenchymal transition (EMT) by profiling a gene expression signature using a targeted sequencing platform, the RASL-Seq assay. The presence of CTCs that have undergone EMT is prognostic of poor long term survival. The gene profile will also include genes for identifying and counting EpCAM+ and EpCAM- CTCs, and for identifying the expression of targets for therapeutic agents. Thus, the RASL-Seq CTC Profiling signature assay will deliver the EpCAM+ counts that the current Veridex CellSearch(R) assay does, but provide significant additional utility by identifying EpCAM- cells that have undergone EMT (not assessed by CellSearch) and which put the patient at risk, as well as provide the oncologist with an indication of what therapy these cells may be responsive to, overall significantly improving patient care and survival outcome. The EMT and risk signature used in this proposal is the subject of patents filed by MD Anderson. BioSpyder, which has separately licensed the RASL-Seq technology from UCSD, will demonstrate its feasibility in Phase I, determining if gene expression profiling of individual CTCs is required or if pools of (e.g. EpCAM- and EpCAM+) CTCs can be used for testing. Initial development and validation will be with cell lines, then a set of 30 patient samples, and finally a set of 200 patient samples. CellSearch results for these patients will be compared to the RASL-Seq assay results to determine the positive predictive value of the RASL-Seq test for Epcam+ CTCs. The results of this program will demonstrate that the RASL-Seq profiling assay has broad applicability not just to CTC analysis, but to analysis of biopsies, and for use as a companion diagnostic.

描述（由申请人提供）：该项目将证明通过使用靶向测序平台 RASL-Seq 分析分析基因表达特征来鉴定经历上皮间质转化 (EMT) 的循环肿瘤细胞 (CTC) 的可行性。经历过 EMT 的 CTC 的存在预示着长期生存不佳。基因谱还将包括用于识别和计数 EpCAM+ 和 EpCAM-CTC 以及用于识别治疗剂靶标表达的基因。因此，RASL-Seq CTC 分析特征分析将提供当前 Veridex CellSearch(R) 分析所提供的 EpCAM+ 计数，但通过识别已经历 EMT（未经 CellSearch 评估）的 EpCAM- 细胞（未由 CellSearch 评估）并放置为处于危险中的患者提供信息，并为肿瘤学家提供这些细胞可能对哪种疗法有反应的指示，总体上显着改善患者护理和生存结果。本提案中使用的 EMT 和风险签名是 MD 安德森申请专利的主题。 BioSpyder 已从 UCSD 单独获得 RASL-Seq 技术许可，将在第一阶段展示其可行性，确定单个 CTC 的基因表达谱是否有效是必需的或者是否可以使用 CTC 池（例如 EpCAM- 和 EpCAM+）进行测试。最初的开发和验证将使用细胞系，然后是一组 30 个患者样本，最后是一个一组 200 个患者样本。这些患者的 CellSearch 结果将与 RASL-Seq 检测结果进行比较，以确定 RASL-Seq 检测对 Epcam+ CTC 的阳性预测值。该计划的结果将证明 RASL-Seq 分析测定不仅具有广泛的适用性，不仅适用于 CTC 分析，而且适用于活检分析，并可用作伴随诊断。