: 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).
Public Health Relevance Statement: Project Narrative Cancer is a leading cause of death and suffering in the United States and worldwide, and cancer recurrence or progression after treatment, or unintended side-effects and complications resulting from treatment that is no longer effective, can both contribute to suffering and early demise. Detection of rare cancer cells in circulation via a routine blood draw is called a "liquid biopsy," and can inform early intervention or change of treatment to a more effective form, while avoiding harm and costs from ineffective treatment; TelomeScan is a unique liquid biopsy assay that specifically detects circulating cancer cells (CTCs) by an elevated telomerase activity signature, characteristic of nearly all types of cancer but not normal cells. The development of TelomeScan into an effective commercial product could greatly aid the treatment and management of a wide variety of solid cancers (such as lung cancer) and help cancer patients worldwide, enhancing treatment success and patient survival while minimizing unnecessary harm and costs of ineffective treatment.
Project Terms: Academia; Detection; Cancer Diagnostics; Mesenchymal; Reproducibility; Cancer Center; Cancer Detection; Cancer Patient; Cellular Assay; cell assay; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; validations; Monitor; Characteristics; Molecular; Process; epithelial to mesenchymal transition; Development; developmental; Image; imaging; uterine and cervical cancer; cervical and uterine cancer; pilot trial; cost; next generation; Population; cancer type; innovate; innovative; innovation; resistant; Resistance; prototype; commercialization; tumor; clinical care; response to therapy; response to treatment; therapeutic response; therapy response; treatment response; bio-markers; biologic marker; biomarker; Biological Markers; targeted drug therapy; targeted drug treatments; targeted therapeutic; targeted therapeutic agents; targeted therapy; targeted treatment; B7-H1; B7H1; CD274; PD-L1; PDL-1; PDL1; Programmed Cell Death 1 Ligand 1; Programmed Death Ligand 1; programmed cell death protein ligand 1; protein death-ligand 1; programmed cell death ligand 1; Academic support; microscope imaging; microscopy imaging; microscopic imaging; CLIA accredited; CLIA approved; CLIA compliant; CLIA licensed; CLIA certified; ineffective treatment; ineffective therapies; liquid biopsy; Checkpoint inhibitor; immune check point inhibitor; Immune checkpoint inhibitor; cancers that are rare; rare malignancy; rare tumor; rare cancer; automated analysis; side effect; Multi-center clinical study; Multicenter clinical study; Multisite clinical study; Multi-site clinical study; lung cancer cell; Circulation; Acceleration; accredited; Accreditation; Adenoviridae; Adenoviruses; After Care; After-Treatment; post treatment; Aftercare; Biological Assay; Assay; Bioassay; Biologic Assays; Biopsy; Biotechnology; Biotech; Blood; Blood Reticuloendothelial System; Brain Neoplasms; Brain Neoplasia; Brain Tumors; tumors in the brain; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Non-Small-Cell Lung Carcinoma; NSCLC; NSCLC - Non-Small Cell Lung Cancer; Non-Small Cell Lung Cancer; Nonsmall Cell Lung Carcinoma; Cause of Death; Cells; Cell Body; Clinical Research; Clinical Study; Clinical Trials; Cessation of life; Death; Decision Making; Diagnostic Imaging; Down-Regulation; Edema; Dropsy; Hydrops; Eligibility Determination; Eligibility; Protocol Screening; Genes; Genetic Engineering; Genetic Engineering Biotechnology; Genetic Engineering Molecular Biology; Recombinant DNA Technology; genetically engineered; Goals; Head and Neck Neoplasms; head and neck tumor; Human; Modern Man; Immunotherapy; Immune mediated therapy; Immunologically Directed Therapy; immune therapeutic approach; immune therapeutic interventions; immune therapeutic regimens; immune therapeutic strategy; immune therapy; immune-based therapies; immune-based treatments; immuno therapy; Inflammation; Laboratories; Lead; Pb element; heavy metal Pb; heavy metal lead; Longitudinal Studies; long-term study; longitudinal outcome studies; longterm study; melanoma; Malignant Melanoma; Methods; Morbidity - disease rate; Morbidity; Neoplasm Circulating Cells; circulating neoplastic cell; circulating tumor cell; Neoplasm Metastasis; Metastasis; Metastasize; Metastatic Lesion; Metastatic Mass; Metastatic Neoplasm; Metastatic Tumor; Secondary Neoplasm; Secondary Tumor; cancer metastasis; tumor cell metastasis; Patients; Pennsylvania; Physicians; Proteins; Publishing; Radiation therapy; Radiotherapeutics; Radiotherapy; radiation treatment; treatment with radiation; Recurrence; Recurrent; Repeat Surgery; Reoperation; RNA-Directed DNA Polymerase; EC 2.7.7.49; RNA Transcriptase; RNA-Dependent DNA Polymerase; Reverse Transcriptase; Revertase; Risk; Signal Transduction; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Specificity; Stains; Staining method; Technology; Testing; Time; Translations; translation; United States; Universities; Work; Telomerase; Treatment Cost; Green Fluorescent Proteins; cancer progression; neoplasm progression; neoplastic progression; tumor progression; improved; Procedures; Solid; Clinical; Phase; Epithelium; peripheral blood; Malignant Tumor of the Lung; Pulmonary Cancer; Pulmonary malignant Neoplasm; lung cancer; Malignant neoplasm of lung; Early Intervention; Oncology Cancer; Oncology; Collaborations; fluid; liquid; Liquid substance; cancer cell; Malignant Cell; Diagnostic; Specimen; Research Specimen; Scientist; Protocols documentation; Protocol; Techniques; Recurrent tumor; Recurrent Neoplasm; neoplasm recurrence; single cell analysis; success; Peripheral Blood Mononuclear Cell; PBMC; novel; Cell surface; Therapeutic Intervention; intervention therapy; Radiation; Sampling; high throughput analysis; software development; develop software; developing computer software; cancer recurrence; circulating cancer cell; protein expression; Normal Cell; image-based method; imaging method; imaging modality; Signaling Protein; Signaling Factor Proto-Oncogene; Signaling Pathway Gene; Recurrent Malignant Neoplasm; Recurrent Cancer; Recurrent Malignant Tumor
