Ferromagnetic Dense Particle-based Early Diagnostic Test for Liver Cancer.?

基于铁磁致密颗粒的肝癌早期诊断测试。

• 批准号: 7669495
• 负责人: Thomas R Russell
• 金额: $ 15.97万
• 依托单位: RUSSELL BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7669495
• 关键词: AFP gene; Address; Alcoholic Liver Diseases; Antibodies; Archives; Biological Assay; Biological Markers; Blinded; Blood specimen; Categories; Cirrhosis; Clinical; Clinical Research; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Early Diagnosis; Excision; Glycoproteins; Gold; Grant; HCV Liver Disease; Healthcare Market; Hepatitis B Virus; Hepatitis C; Hepatitis C virus; Individual; Kinetics; Lead; Lectin; Licensing; Liver; Liver diseases; Malignant Neoplasms; Malignant neoplasm of liver; Marketing; Medical; Patients; Performance; Phase; Predictive Value; Process; Prospective Studies; Protein Binding; Proteins; Protocols documentation; Reaction; Research Design; Sampling; Screening for Hepatocellular Cancer; Screening procedure; Sensitivity and Specificity; Serum; Signal Transduction; Small Business Innovation Research Grant; Specificity; Staging; Survival Rate; System; Technology; Testing; Time; Viral; Whole Blood; Work; base; cancer risk; cohort; commercialization; cost; early onset; effective intervention; high throughput screening; improved; meetings; non-alcoholic; novel; particle; patient population; public health relevance; validation studies

DESCRIPTION (provided by applicant): The aim of this project is to determine if an assay using ferromagnetic dense particles (FDP) can improve the detection of the fucosylated glycoforms of secreted liver biomarkers that are present only at very low levels in early-stage liver cancer (HCC) patient serum. Advantages of the FDP format include: very high protein binding capacity, very high mixing efficiency, very rapid reaction kinetics, minimal non-specific interference, and the ability to use unprocessed whole blood samples in a commercial clinical setting. FDP is expected to avoid loss/degradation of rare biomarker species during sample processing and eliminate non-specific interference. The results will be a rapid, accurate, easy to use screening test with a minimal number of processing steps. Thus the aims of this phase I SBIR are to develop a system to neutralize the interference of heterophilic anti-gal antibodies and to develop and optimize an FDP-based assay for three fucosylated biomarkers of HCC using archived serum samples. In Phase II we will further optimize the test for use with unprocessed whole blood and generate a simple to use, rapid and sensitive HCC test to satisfy an important medical need to recognize this highly lethal disease at the earliest possible time. Our commercial objective is to license the validated assay to a clinical diagnostics company that can adapt our FDP-based test to a commercial clinical format, obtain regulatory approval, market and distribute the first reliable and accurate early-detection assay for HCC to the healthcare market. We firmly believe that this phase I proposal will develop an assay robust enough to be used for high throughput screening of patients for the early onset of HCC based on our previous work. Thus, at the conclusion of this project, we strongly believe that we will have developed an FDP-based assay format with our three biomarkers that will allow us to detect liver cancer with >95% sensitivity and >95% specificity, which is substantially better than the current marker AFP, when used alone. Thus, using FDP separation technology in combination with Dr. Mehta's unique biomarkers, specific whole blood diagnostic tests will be developed to meet this underserved medical need. Aim 1. Develop a high throughput ferromagnetic particle (FDP)-based assay to remove heterophilic anti-gal antibodies from serum (6 months).Aim 2. Develop a high throughput ferromagnetic particle (FDP)-based assay to quantitatively capture and detect serum levels of four fucosylated protein biomarkers that are positively correlated with the early stage development of liver cancer and perform a pre-validation study using a broader patient population. PUBLIC HEALTH RELEVANCE: There is a significant unmet medical need for the early detection of liver cancer (HCC) as 5 year survival rates are extremely low. The proposal outlined in this SBIR grant addresses this need. The combination of Russell Biotech's novel FDP separation technology with the biomarkers identified by Dr. Mehta will lead to very rapid, sensitive diagnostic test(s) for the early detection of this devastating cancer.

描述（由申请方提供）：本项目的目的是确定使用铁磁致密颗粒（FDP）的检测方法是否可以改善分泌型肝脏生物标志物的岩藻糖基化糖型的检测，这些生物标志物仅以极低水平存在于早期肝癌（HCC）患者血清中。FDP格式的优点包括：非常高的蛋白结合能力、非常高的混合效率、非常快的反应动力学、最小的非特异性干扰以及在商业临床环境中使用未处理的全血样本的能力。预计FDP可避免样品处理期间稀有生物标志物物种的损失/降解，并消除非特异性干扰。结果将是一个快速，准确，易于使用的筛选测试与最少的处理步骤。因此，该I期SBIR的目的是开发一种系统，以中和异嗜性抗gal抗体的干扰，并开发和优化基于FDP的测定法，用于使用存档的血清样品测定HCC的三种岩藻糖基化生物标志物。在第二阶段，我们将进一步优化用于未处理全血的检测，并产生一种简单易用、快速灵敏的HCC检测，以满足尽早识别这种高致命性疾病的重要医疗需求。我们的商业目标是将经过验证的检测方法授权给一家临床诊断公司，该公司可以将我们基于FDP的检测方法应用于商业临床形式，获得监管机构的批准，向医疗保健市场销售和分销第一个可靠和准确的HCC早期检测方法。我们坚信，基于我们以前的工作，这一I期提案将开发出一种足够稳健的检测方法，用于高通量筛查早期HCC患者。因此，在该项目结束时，我们坚信，我们将开发出一种基于FDP的检测形式，使用我们的三种生物标志物，使我们能够以>95%的灵敏度和>95%的特异性检测肝癌，这比单独使用时的当前标志物AFP要好得多。因此，使用FDP分离技术结合Mehta博士独特的生物标志物，将开发特定的全血诊断测试，以满足这一服务不足的医疗需求。目标1.建立一种高通量的铁磁颗粒（FDP）检测方法，用于去除血清中的异嗜性抗半乳糖抗体（6个月）。开发基于高通量铁磁颗粒（FDP）的检测方法，以定量捕获和检测与肝癌早期发展呈正相关的四种岩藻糖基化蛋白生物标志物的血清水平，并使用更广泛的患者人群进行预验证研究。公共卫生相关性：对于肝癌（HCC）的早期检测存在显著未满足的医疗需求，因为5年存活率极低。SBIR赠款中概述的提案解决了这一需求。罗素生物技术公司的新型FDP分离技术与梅塔博士鉴定的生物标志物相结合，将导致非常快速，灵敏的诊断测试，用于早期检测这种毁灭性的癌症。