Minimal Residual Disease Monitoring by T-cell Receptor Repertoire Profiling

描述（由申请人提供）：通过T细胞受体谱系进行的微小残留疾病监测分析T细胞肿瘤通常比类似的B细胞淋巴瘤更具侵袭性，并且预后较差。此外，对于这些患者中的许多人来说，疾病复发后的预后是令人沮丧的。检测治疗后是否存在微小残留病（MRD）正在成为一种对复发风险进行分层和个性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，这些检测方法只能可靠地检测1：100至1：10，000细胞范围内的MRD，因此只有在恶性细胞达到可感知的频率，超过治疗可能最有效的点时，才有可能进行检测。 在此，我们提出了一种新的方法，用于识别肿瘤淋巴细胞群体和测量MRD的T细胞受体（TCR）库的直接测序，使用我们建立的高通量T细胞受体测序技术。我们的半定量技术非常灵敏，可以检测到低于1：100，000细胞的克隆（比标准方法灵敏度提高10倍）。该方法将通过使用来自成熟T细胞淋巴瘤患者队列的样本的合作项目进一步开发和验证潜在的临床应用。本研究的结果不仅与T细胞肿瘤中MRD的评估相关;其扩展至B细胞肿瘤中MRD的检测将扩大本试验对所有血液学肿瘤的适用性。

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.