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

一种创新的端粒酶靶向循环肿瘤细胞检测方法，用于监测接受放射和免疫疗法治疗的非小细胞肺癌

• 批准号: 10546634
• 负责人: Deeksha Saxena
• 金额: $ 39.95万
• 依托单位: LIQUID BIODX LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546634
• 关键词: Academia; Academic support; Acceleration; Accreditation; Adenoviruses; Aftercare; Biological Assay; Biological Markers; Biopsy; Biotechnology; Blood; Brain Neoplasms; CLIA certified; Cancer Center; Cancer Detection; Cancer Diagnostics; Cancer Patient; Cause of Death; Cell surface; Cells; Cellular Assay; Cessation of life; Characteristics; Circulation; Clinical; Clinical Research; Clinical Trials; Collaborations; Decision Making; Detection; Development; Diagnostic; Diagnostic Imaging; Down-Regulation; Early Intervention; Edema; Eligibility Determination; Epithelium; Genes; Genetic Engineering; Goals; Green Fluorescent Proteins; Head and Neck Neoplasms; Human; Image; Immune checkpoint inhibitor; Immunotherapy; Inflammation; Laboratories; Lead; Liquid substance; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of lung; Mesenchymal; Methods; Molecular; Monitor; Morbidity - disease rate; Multi-site clinical study; Neoplasm Circulating Cells; Neoplasm Metastasis; Non-Small-Cell Lung Carcinoma; Normal Cell; Oncology; Patients; Pennsylvania; Peripheral Blood Mononuclear Cell; Phase; Physicians; Population; Procedures; Process; Proteins; Protocols documentation; Publishing; RNA-Directed DNA Polymerase; Radiation; Radiation therapy; Recurrence; Recurrent Malignant Neoplasm; Recurrent tumor; Repeat Surgery; Reproducibility; Resistance; Risk; Sampling; Scientist; Signal Transduction; Signaling Protein; Small Business Innovation Research Grant; Solid; Specificity; Specimen; Stains; Techniques; Technology; Telomerase; Testing; Therapeutic Intervention; Time; Translations; Treatment Cost; United States; Universities; Validation; Work; automated analysis; cancer cell; cancer recurrence; cancer type; cervical and uterine cancer; circulating cancer cell; clinical care; commercialization; cost; epithelial to mesenchymal transition; high throughput analysis; imaging modality; improved; ineffective therapies; innovation; liquid biopsy; lung cancer cell; melanoma; microscopic imaging; next generation; novel; peripheral blood; pilot trial; programmed cell death ligand 1; protein expression; prototype; rare cancer; side effect; single cell analysis; software development; success; targeted treatment; treatment response; tumor; tumor progression

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).

项目概要： 癌症是美国和全世界死亡的主要原因， 每年有100万人死亡。治疗后延迟检测癌症进展或复发 导致发病率增加和快速死亡，但由于 严重的风险。常规成像模式用于及时检测的准确性是有限的，特别是在 放射和免疫疗法，当治疗诱导的水肿/炎症模拟癌症进展时。因此，在本发明中， 迫切需要安全、可靠和非侵入性的连续生物标记物（“液体活组织检查”），其提供“真实的- 时间”信息的状态，广泛的固体癌症。Liquid Biotech与学术界合作， 和NRG癌症合作组开发TelomeScan循环肿瘤细胞（CTC）检测， 这些未满足的需求。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）在活癌细胞（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 EMT（EMT）是癌症中常见的一种。TelomeScan一直显示它可以检测癌症 非小细胞肺癌（NSCLC）患者在常规化疗前6个月至2年复发 诊断成像，从而为可行的治疗干预提供宝贵的前置时间，同时最大限度地减少 意外的副作用和不再有效的治疗费用。液体生物技术公司继续在这些 通过在中心实验室提供用于多中心临床研究的检测试剂盒，我们 目前正在完成另外两项临床试验，包括与NRG合作的NSCLC临床试验 肿瘤科该项目的目标是将TelomeScan开发成一种商业化产品， 使更多的患者受益。Aim 1将开发一种临床原型，用于端粒扫描测试， 自动化分析，以处理大量的样本，从而扩大访问和癌症 覆盖目的2将开发端粒扫描鉴定的NSCLC细胞中PD-L1染色的定量， CTC，通过监测来自接受或符合放射条件的患者的治疗前和治疗后样本， 免疫疗法这些目标将扩大获得，使更多的NSCLC患者受益 和其他癌症（第二阶段）。