Integrated Systems for the Analysis of Circulating Multiple Myeloma Cells (CMMCs)

用于分析循环多发性骨髓瘤细胞 (CMMC) 的集成系统

• 批准号: 9048507
• 负责人: Mateusz Lukasz Hupert
• 金额: $ 80.9万
• 依托单位: BIOFLUIDICA, INC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-24 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9048507
• 关键词: Age; American Cancer Society; Antibodies; Architecture; Automation; Biological; Biological Assay; Biological Markers; Blood; Blood specimen; Bone Marrow; Bone marrow biopsy; Case Study; Cell Count; Cell Separation; Cells; Cessation of life; Chromosome abnormality; Chromosomes, Human, Pair 13; Clinical; Color; Computer software; Cytogenetic Analysis; Cytogenetics; Cytometry; DNA Sequence Alteration; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Electronics; Fluorescent in Situ Hybridization; Future; Gene Expression; Goals; Hematopoietic Neoplasms; Housing; Image; Image Analysis; Immunophenotyping; In Situ Hybridization; Individual; Injection of therapeutic agent; KRAS2 gene; Label; Laboratories; Ligase; Light; Liquid substance; Location; Malignant Neoplasms; Measures; Mechanics; Microscope; Microscopy; Molds; Molecular Profiling; Monitor; Monoclonal gammopathy of uncertain significance; Morphology; Multiple Myeloma; Mutation; NCAM1 gene; Neoplasm Circulating Cells; North Carolina; Oncologist; Optics; Outcome; Pain; Patients; Performance; Peripheral; Pharmaceutical Preparations; Phase; Phenotype; Pilot Projects; Plasma Cells; Point Mutation; Prevalence; Process; Production; Protocols documentation; Reaction; Recovery; Recurrence; Reporting; Risk; Running; Sales; Sampling; Secure; Serum; Staging; Staining method; Stains; System; Systems Analysis; Techniques; Testing; Therapeutic; Time; Translations; Universities; Validation; Whole Blood; base; commercialization; cost; design; electric impedance; experience; fluorescence microscope; improved; innovation; instrument; instrumentation; multiple myeloma M Protein; novel; operation; outcome forecast; peripheral blood; phase 2 study; programs; prototype; public health relevance; research and development; research study; response; validation studies

 DESCRIPTION (provided by applicant): Multiple myeloma (MM) is a plasma cell malignancy and comprises about 1% of malignant tumors and 15% of all hematopoietic neoplasms. According to the American Cancer Society, in 2014 an estimated 24,050 new cases were diagnosed in the U.S. with the estimated deaths being 11,090. Monoclonal gammopathy of undetermined significance (MGUS) is associated with a 1% per year risk of progression to overt malignancy, most commonly MM and is found in approximately 3% of individuals over 50 with the prevalence increasing with age. Without a clear diagnostic test to monitor MGUS malignancy progression, a range of factors are currently monitored including changes in serum free light chains ratio, elevated serum M protein level and high bone marrow plasma cell percentage . Recent studies have demonstrated that circulating multiple myeloma cells (CMMCs) secured from bone marrow biopsies measured by immuno-fluorescence microscopy or flow cytometry are useful for diagnosis, prognosis and measuring therapeutic response for MM. However, securing a bone marrow biopsy is painful to the patient prohibiting frequent testing required for monitoring disease progression, drug response and/or recurrence. Development of novel instrumentation and techniques for CMMC selection and analysis directly from peripheral blood is essential to improve the management of patients with MM or its early disease stages. Building on extensive preliminary data secured from a Phase I type study, this Phase II project is focused on the development of an integrated system that uses a disposable fluidic cartridge and the associated instrument peripherals for the rapid and fully automated processing of CMMCs directly from whole blood obviating the need for bone marrow biopsies and thus, allowing for more frequent testing especially those with MGUS. The instrument will be able to select CMMCs at >80% recovery and >80% purity, release the selected cells and electronically enumerate them and prepare them for FISH analysis or immunophenotyping. The system can also off-load the selected CMMCs for molecular profiling, such as searching for KRAS mutations. Operation of the instrument will be automated with an overall sample- to-answer processing time of ~1.5 h. The system will be subjected to both internal validation by BioFluidica staff as well as external validation by collaborators at the University of North Carolina at Chapel Hill. While MM will be used as a case study for clinical performance verification of the instrument, it can easily be utilized in different cancer-related diseases by programming in the correct selection antibody to search for the relevant blood-borne biological cells.

 描述（由适用提供）：多发性骨髓瘤（MM）是血浆细胞恶性肿瘤，约占恶性肿瘤的1％和所有造血性肿瘤的15％。根据美国癌症学会的数据，2014年在美国诊断出大约24,050例新病例，估计死亡为11,090例。不确定意义（MGU）的单克隆性伽马病（MGU）与每年1％的疾病风险相关，最常见的是MM，并且在大约50岁以上的个人中发现，随着年龄的增长，患病率增加。如果没有明确的诊断测试来监测MGUS恶性肿瘤的进展，目前监视了一系列因素，包括血清游离光链比的变化，血清M蛋白水平升高和高骨髓浆细胞百分比。最近的研究表明，通过免疫荧光显微镜或流动细胞仪测量的骨髓活检中循环多个骨髓瘤细胞（CMMC）对诊断，预后和测量MM的治疗反应有用。然而，确保骨髓活检对患者的禁止经常进行监测疾病进展，药物反应和/或复发所需的经常测试。直接从外周血选择和分析CMMC选择和分析的新型仪器和技术的开发对于改善MM或其早期疾病阶段的患者的治疗至关重要。该II期项目的基础是从I期类型研究中获得的广泛初步数据，重点是开发一种综合系统，该系统使用一次性液体弹药筒和相关的仪器外围设备，用于直接从全血中快速且完全自动化的CMM处理，从而使全血只是避免了对骨骨髓活检的需求，从而可以更常见地进行测试，从而尤其是那些经常进行测试。该仪器将能够以> 80％的回收率和> 80％的纯度选择CMMC，释放选定的细胞并以电子方式列举它们，并为它们做好准备以进行鱼类分析或免疫表型。该系统还可以将所选的CMMC卸载进行分子分析，例如搜索KRAS突变。该仪器的运行将以约1.5 h的整体样品处理时间自动化。该系统将受到Biofluidica员工的内部验证，以及北卡罗来纳大学教堂山分校的合作者的外部验证。虽然MM将用作仪器临床性能验证的案例研究，但可以通过在正确的选择抗体中编程来搜索相关的血传播生物学细胞，从而在不同的癌症相关疾病中很容易使用。