Minimal Residual Disease Monitoring by T-cell Receptor Repertoire Profiling

通过 T 细胞受体库分析进行最小残留疾病监测

• 批准号: 8455699
• 负责人: MARK J RIEDER
• 金额: $ 16.52万
• 依托单位: ADAPTIVE BIOTECHNOLOGIES CORPORATION
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-24 至 2013-12-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8455699
• 关键词: Aftercare; B-Cell Lymphomas; B-Cell Neoplasm; Biological Assay; Cancerous; Cells; Clinical; Detection; Detection of Minimal Residual Disease; Diagnosis; Flow Cytometry; Frequencies; Gene Rearrangement; Goals; Hematologic Neoplasms; Incidence; Individual; Lymphoblastic Leukemia; Lymphoid; Lymphoma; Malignant - descriptor; Malignant Neoplasms; Mature T-Lymphocyte; Measurable; Measures; Methods; Molecular; Monitor; Neoplasms; Outcome; Patients; Phase; Population; Recurrent disease; Refractory Disease; Relapse; Reproducibility; Research Infrastructure; Residual Neoplasm; Risk; Risk Factors; Sampling; Severity of illness; Small Business Innovation Research Grant; T-Cell Lymphoma; T-Cell Receptor; T-Cell Receptor Genes; T-Cell and NK-Cell Neoplasm; T-Lymphocyte; Technology; Time; base; cancer cell; clinical application; cohort; indexing; leukemia; leukemia/lymphoma; neoplastic; outcome forecast; prognostic; public health relevance; screening; standard measure

DESCRIPTION (provided by applicant): Minimal Residual Disease Monitoring by T-cell Receptor Repertoire Profiling T-cell neoplasms are generally more aggressive and have poorer outcomes than comparable B-cell lymphomas. In addition, for many of these patients, prognosis following disease relapse is dismal. Detecting the presence or absence of Minimal Residual Disease (MRD) following treatment is emerging as an alternative method to stratify relapse risk and individualize patient treatment. Depending on the type of T cell malignancy, a number of methods are clinically used to detect MRD. However, these assays can only reliably detect MRD in the range of 1:100 to 1:10,000 cells, thus detection is only possible once malignant cells have reached an appreciable frequency, past the point where treatment could be most effective. Herein, we propose a new method for identifying neoplastic lymphoid populations and measuring MRD by direct sequencing of the T-cell receptor (TCR) repertoire using our established high-throughput T-cell receptor sequencing technology. Our semi-quantitative technology is sensitive and can detect clones down to fewer than 1:100,000 cells (10-fold increased sensitivity over standard methods). This method will be further developed and validated for potential clinical applications through a collaborative project using samples from a cohort of mature T-cell lymphoma patients. The findings from this study will not only be relevant for assessment of MRD in T-cell neoplasms; its extension to the detection of MRD in B-cell neoplasms will expand the applicability of this assay to all hematological neoplasms.

描述（由申请人提供）：通过t细胞受体库谱检测微小残留疾病t细胞肿瘤通常比类似的b细胞淋巴瘤更具侵袭性，预后较差。此外，对于这些患者中的许多人，疾病复发后的预后是令人沮丧的。治疗后检测微量残留病（MRD）的存在或不存在正成为复发风险分层和个体化患者治疗的替代方法。根据T细胞恶性肿瘤的类型，临床上使用许多方法来检测MRD。然而，这些检测只能可靠地检测1:100到1:10 000细胞范围内的MRD，因此只有当恶性细胞达到可察觉的频率，超过治疗可能最有效的点时才有可能检测。在此，我们提出了一种新的方法，通过使用我们建立的高通量t细胞受体测序技术对t细胞受体（TCR）库进行直接测序来鉴定肿瘤淋巴细胞群和测量MRD。我们的半定量技术非常敏感，可以检测到小于1:10万细胞的克隆（灵敏度比标准方法提高了10倍）。该方法将通过一个合作项目进一步开发和验证潜在的临床应用，该项目将使用来自成熟t细胞淋巴瘤患者队列的样本。这项研究的结果不仅与t细胞肿瘤的MRD评估相关；将其扩展到b细胞肿瘤的MRD检测，将扩大该方法对所有血液肿瘤的适用性。