Biomechanical enrichment of malignant cells enabling companion diagnostics

恶性细胞的生物力学富集实现伴随诊断

• 批准号: 8782408
• 负责人: Henry Tse
• 金额: $ 35万
• 依托单位: CYTOVALE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-10 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8782408
• 关键词: Antigens; Antineoplastic Agents; Benign; Biological Assay; Biological Markers; Biomechanics; Biopsy; Blood; Blood Cells; Breast; Caliber; Cancer Patient; Cancer cell line; Cell Extracts; Cell Line; Cell Separation; Cell Size; Cell surface; Cells; Clinical; Clinical Research; Companions; Cytometry; Data; Detection; Diagnosis; Diagnostic; Diagnostic tests; Distant; Evaluation; Excision; Fractionation; Gene Mutation; Genetic; Genetic screening method; Goals; Injection of therapeutic agent; Knowledge; Label; Lesion; Leukocytes; Liquid substance; Lung; Malignant Neoplasms; Masks; Measures; Mechanics; Mesothelial Cell; Methods; Microfluidics; Micrometastasis; Modeling; Molds; Molecular; Mutation; Nodule; Normal Cell; Organ; Outcome; Patients; Peritoneal Fluid; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physiological; Pleural; Pleural cavity; Pleural effusion disorder; Point Mutation; Population; Population Distributions; Predisposition; Primary Neoplasm; Property; Reporting; Resistance; Sampling; Science; Sensitivity and Specificity; Shapes; Signal Transduction; Site; Solutions; Sorting - Cell Movement; Source; Specimen; Stress; Stretching; System; Techniques; Technology; Tumor Tissue; Urine; base; biophysical properties; cancer cell; cancer therapy; cost; design; effusion; improved; instrument; interest; malignant phenotype; meetings; neoplastic cell; particle; physical property; public health relevance; success; translational medicine; tumor; tumorigenic

DESCRIPTION (provided by applicant): The rise in using companion diagnostics to guide selection of pharmacological agents in cancer treatment has led to a need for technologies which can extend these diagnostics to additional patients with difficult to access tumors. Such diagnostic assays are performed on cells extracted from tumors or metastatic cells found distant from the primary tumor site. Evaluation of bodily fluids, including blood, urine, effusions, for disseminated malignant cells originating from the lung, breast or other organs is an alternative to examination of primary tumor tissue, especially when biopsy is not possible at the primary tumor site. For example, pleural effusions, which can be the first presentation of a patient's cancer and thus contain some of the most diagnostically relevant cells, could be used as an easily accessible source of malignant cells to assay specific genetic lesions indicative of susceptibility to targeted therapies. However, the accuracy of these assays is limited by the presence of a large background of normal cells. Current approaches for enriching malignant cells from bodily fluids for these assays can require prior knowledge about the type of malignancy, which is often unavailable, or result in insufficient purity (<40%) for confident diagnoses. Biophysical properties of cells have been shown to be extremely specific label-free biomarkers of malignant phenotypes. Here, we aim to develop an instrument which will isolate target cancer cells using a combination of intrinsic physical biomarkers associated with malignancy - cell size and deformability - with high yield and purity. CytoVale is commercializing a technology, 'deformability cytometry', which assays the biophysical properties of thousands of cells per second and has demonstrated utility in diagnosing malignancy in pleural effusions. Expanding upon its core technology, CytoVale will, in this project, develop an instrument which will be able to isolate malignant cells for companion diagnostic assays, from large volumes of bodily fluids, with higher sensitivity and specificity than currently available techniques. This wil increase the accessibility of these powerful assays which have demonstrated immense clinical success in recent years, thereby improving patient outcomes.

描述（由申请人提供）：在癌症治疗中使用伴随诊断来指导药理学试剂选择的兴起导致需要能够将这些诊断扩展到难以进入肿瘤的其他患者的技术。对从远离原发性肿瘤部位的肿瘤或转移性细胞提取的细胞进行此类诊断测定。评估体液（包括血液、尿液、渗出液）中是否存在源自肺、乳腺或其他器官的播散性恶性细胞是检查原发性肿瘤组织的替代方法，尤其是在原发性肿瘤部位无法进行活检时。例如，胸腔积液可以是患者癌症的第一表现，因此含有一些诊断上最相关的细胞，可以用作容易获得的恶性细胞来源，以测定指示对靶向治疗敏感性的特定遗传病变。然而，这些测定的准确性受到存在大量正常细胞背景的限制。目前从体液中富集恶性细胞用于这些测定的方法可能需要关于恶性肿瘤类型的先验知识，这通常是不可用的，或者导致纯度不足（<40%）而无法进行可靠的诊断。细胞的生物物理特性已被证明是恶性表型的极其特异的无标记生物标志物。在这里，我们的目标是开发一种仪器，该仪器将使用与恶性肿瘤相关的内在物理生物标志物-细胞大小和变形性-以高产率和纯度分离靶癌细胞。CytoVale正在商业化一项技术，“变形性细胞仪”，该技术每秒检测数千个细胞的生物物理特性，并已证明可用于诊断胸腔积液中的恶性肿瘤。在该项目中，CytoVale将扩展其核心技术，开发一种能够从大量体液中分离恶性细胞用于伴随诊断分析的仪器，其灵敏度和特异性高于目前可用的技术。这将增加这些强大的检测的可及性，这些检测在近年来已经证明了巨大的临床成功，从而改善患者的结果。