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).