HHSN261201400050C;TOPIC 309?DEVELOPMENT OF LOW COST, SMALL SAMPLE MULTI-ANALYTE TECH. FOR CANCER DIAGNOSIS,PROGNOSIS&EARLY DETECTION?;TITLE:HIGHLY SENSITIVE AND SPECIFIC MULTIPLEX PROSTATE CANCER ASSA

HHSN261201400050C；主题309？低成本、小样本多分析技术的开发。

• 批准号: 8942373
• 负责人: WLODEK MANDECKI
• 金额: $ 99.84万
• 依托单位: PHARMASEQ, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-16 至 2016-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8942373
• 关键词: Annexin A3; Biological Assay; Biological Markers; Cancer Diagnostics; Cancer Patient; Custom; Detection; Development; Diagnostic; Early Diagnosis; Elements; Endoglin; Evaluation; Fluorescence; Frequencies; Goals; Interleukin-8; Intervention; Life Style; Light; Malignant neoplasm of prostate; Metals; Methods; PLAB Protein; Performance; Phase; Prostate-Specific Antigen; Radio; Sampling; Serum; Silver; Societies; Specificity; Testing; Urine; Work; assay development; base; cancer diagnosis; clinically significant; cost; cost effective; improved; innovation; instrumentation; outcome forecast; phase 1 study; phase 2 study; preclinical study; success

The main goal of the Phase II project is to build on the success of the Phase I study to develop a cost-effective multiplex serum assay with an expanded biomarker panel for detection of clinically significant forms of prostate cancer (PCa), and perform a larger scale preclinical study of the assay using PharmaSeq's p-Chip-based platform. In the Phase I study of 70 PCa serum samples, we determined that Macrophage Inhibitory Cytokine 1 (MIC-l) has promise for prostate cancer diagnosis and that including serum levels of MIC-l with prostate specific antigen (PSA) improves specificity of PCa diagnosis without compromising the high sensitivity of the PSA test. In the Phase II study, we propose to expand the panel of markers in the PCa assay to include, in addition to MIC-l, Endoglin, Interleukin-8 (IL-8) and Annexin A3. The latter three biomarkers were previously used in a multiplex urine assay, and when combined, were found to significantly outperform the current serum PSA test for PCa diagnosis (a recent study at PharmaSeq and JHUSOM). The benefits of using the four biomarkers will be evaluated in the multiplex serum-based assay at JHUSOM and at PharmaSeq. Silver nanolayer-based metal-enhanced fluorescence was demonstrated to provide an ultrasensitive assay in the Phase I study and will be applied in the Phase II work, if needed. The multiplex assay is adapted to PharmaSeq's innovative platform, the key element of which is the p-Chip, a unique RFID microtransponder, which is capable of transmitting its ID via radio frequency upon being activated by light. The readout is performed on a custom fluidics-based analyzer for p-Chips that simultaneously determines the fluorescence intensity and the p-Chip ID. The following tasks will be performed: 1) final development of assay and instrumentation, 2) assay qualification and evaluation of performance and 3) preclinical study (proving assay utility in PCa diagnostics) using a larger set of samples. The assay results will be then combined with results of PSA analysis of the samples and used to develop a new calculation method utilizing multiple analytes for PCa diagnosis. The new calculation method is aimed at improving specificity of PCa diagnosis while maintaining high sensitivity of the PSA test to minimize the current high false positive rate. The project is expected to provide a major cost and life style benefit to society: this new multiplex diagnostic assay for PCa could earlier identify clinically significant PCa patients requiring intervention, especially when the results are combined with the routine serum PSA test.

第二阶段项目的主要目标是在第一阶段研究成功的基础上， 用于检测前列腺癌的临床显著形式的具有扩展的生物标志物组的多重血清测定 (PCa)，并使用PharmaSeq的基于p-Chip的平台进行更大规模的临床前研究。在I期 通过对70例PCa血清样本的研究，我们确定巨噬细胞抑制性细胞因子1（MIC-1）有希望用于前列腺 癌症诊断和包括MIC-1与前列腺特异性抗原（PSA）的血清水平提高了PCa的特异性 在不影响PSA测试的高灵敏度的情况下进行诊断。在第二阶段研究中，我们建议扩大 除了MIC-1之外，还包括内皮糖蛋白、白细胞介素-8（IL-8）和膜联蛋白A3。的 后三种生物标志物先前用于多重尿测定，并且当组合时，发现显著地 优于目前用于PCa诊断的血清PSA测试（PharmaSeq和JHUSOM的最近研究）。的好处 将在JHUSOM和PharmaSeq的基于血清的多重测定中评价使用四种生物标志物的结果。银 基于纳米层的金属增强荧光被证明在I期研究中提供了超灵敏的测定 如果需要，将在第二阶段工作中使用。多重检测适用于PharmaSeq的创新平台， 其关键元件是p-Chip，一种独特的RFID微型应答器，能够通过无线电传输其ID 被光激活的频率。在用于p芯片的定制的基于流体学的分析仪上进行读出， 同时测定荧光强度和p-Chip ID。 将执行以下任务：1）测定和仪器的最终开发，2）测定确认 和性能评价，以及3）临床前研究（证明检测试剂盒在PCa诊断中的实用性）， 样品然后将测定结果与样品的PSA分析结果结合，并用于开发新的PSA分析方法。 利用多种分析物进行PCa诊断的计算方法。新的计算方法旨在改善 PCa诊断的特异性，同时保持PSA检测的高灵敏度，以最大限度地减少当前的高假阳性 率该项目预计将提供一个主要的成本和生活方式的好处，以社会：这种新的多重诊断测定 可以更早地识别需要干预的临床显著PCa患者，特别是当结果 结合常规血清PSA检测。