An innovative telomerase-targeted, circulating tumor cell assay for monitoring NSCLC treated with radiation and immunotherapy

项目总结： 癌症是美国和世界各地的主要死亡原因，分别占60多万和8 每年分别有100万人死亡。延迟发现治疗后癌症进展或复发 会增加发病率和迅速死亡，但由于以下原因，再次活组织检查或再次手术通常是不可能的 严重的风险。用于及时检测的传统成像模式的准确性有限，特别是在 放射和免疫疗法，当治疗引起的水肿/炎症模拟癌症进展时。因此， 迫切需要安全、可靠和非侵入性的系列生物标记物(“液体活组织检查”)，以提供“真正的- 时间“信息的状态广泛的固体癌症。Liquid Biotech与学术界合作 和NRG癌症合作小组开发TelomeScan循环肿瘤细胞(CTC)检测，以实现 这些未得到满足的需求。TelomeScan具有独特的优势，包括检测端粒酶活性升高 (这有助于永生，是癌症的标志)活的癌细胞(肿瘤的组成部分， 最直接导致肿瘤进展和转移)，以及对上皮间充质的不渗透性 在癌症中经常发生的过渡(EMT)。TelomeScan一直表明它可以检测到癌症 非小细胞肺癌(NSCLC)患者在常规化疗前6个月至2年的复发 诊断成像，从而为可操作的治疗干预提供宝贵的前期准备时间，同时最大限度地减少 不再有效的意外副作用和治疗费用。Liquid Biotech继续在这些方面 通过在多中心临床研究的中央实验室中提供该分析的可用性。我们是 目前接近完成另外两项临床试验，包括与NRG合作进行的非小细胞肺癌试验 肿瘤学。该项目的目标是将TelomeScan开发成一种商业产品，可以 使更广泛的患者受益。AIM 1将为TelomeScan测试开发临床原型，其中包括 自动化分析可处理数量大得多的样本，从而扩大获取途径并预防癌症 覆盖范围。AIM 2将在TelomeScan鉴定的NSCLC细胞中建立PD-L1染色的定量方法 CTC，通过监测接受或符合放射治疗条件的患者的治疗前和治疗后样本 免疫疗法。这些目标将导致扩大机会，使更多的非小细胞肺癌患者受益 和其他癌症(II期)。

Project Summary: Cancer is a leading cause of death both in the United States and across the world, claiming over 600,000 and 8 million deaths each year, respectively. Delayed detection of cancer progression or recurrence after treatment contributes to increased morbidity and rapid death, but re-biopsy or repeat surgery is usually not possible due to severe risks. The accuracy of conventional imaging modalities for timely detection is limited, especially after radiation- and immunotherapy, when treatment-induced edema/ inflammation mimics cancer progression. Thus, there is an urgent need for safe, reliable, and non-invasive serial biomarkers (“liquid biopsies”) that provide “real- time” information of the status of a wide range of solid cancers. Liquid Biotech has collaborated with academia and NRG cancer cooperative group to develop the TelomeScan circulating tumor cell (CTC) assay for fulfilling these unmet needs. TelomeScan has unique advantages including the detection of elevated telomerase activity (which contributes to immortality and is a hallmark of cancer) in live cancer cells (the component of tumors that most directly lead to tumor progression and metastasis), and imperviousness to the epithelial-mesenchymal transition (EMT) that frequently occurs in cancer. TelomeScan has consistently shown it can detect cancer recurrence in patients with non-small cell lung cancer (NSCLC) six months to 2 years before conventional diagnostic imaging, thus providing valuable lead-time for actionable therapeutic intervention while minimizing unintended side effects and cost of treatment that is no longer effective. Liquid Biotech has continued upon these efforts by providing availability of the assay in a centralized laboratory for multi-center clinical studies. We are currently near completion on two additional clinical trials, including for NSCLC in collaboration with NRG Oncology. The goal of this project is to develop TelomeScan into a commercially available product that can benefit a broader range of patients. Aim 1 will develop a clinical prototype for the TelomeScan test incorporating automated analysis to handle substantially higher volumes of samples, thus expanding access and cancer coverage. Aim 2 will develop the quantification of PD-L1 staining in TelomeScan identified NSCLC cells and CTCs, by monitoring pre- and post-treatment samples from patients undergoing or eligible for radiation and immunotherapy. These aims will lead to expanded access to benefit a far greater number of patients with NSCLC and other cancers (Phase II).