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建立I阶段研究的成功，以发展成本效益 用扩展的生物标志物面板的多重血清测定法检测临床意义的前列腺癌形式 （PCA），并使用Pharmaseq的基于P-CHIP的平台对测定法进行更大的临床前研究。在第一阶段 研究70个PCA血清样品，我们确定巨噬细胞抑制性细胞因子1（MIC-L）有望前列腺 癌症诊断和包括前列腺特异性抗原（PSA）的血清MIC-L水平可提高PCA的特异性 诊断而不损害PSA检验的高灵敏度。在第二阶段研究中，我们建议扩大 PCA测定中的标记面板还包括MIC-L，Endoglin，Interleukin-8（IL-8）和Annexin A3。这 后来的三个生物标志物先前在多重尿液测定中使用，并在合并后显着 优于当前用于PCA诊断的血清PSA检验（Pharmaseq和Jhusom的最新研究）。好处 使用四个生物标志物将在Jhusom和Pharmaseq的多重血清测定中进行评估。银 证明基于纳米层的金属增强荧光可以在I期研究中提供超敏化测定 如果需要，将在第二阶段工作中应用。多重测定法适用于Pharmaseq的创新平台， 其关键要素是P-Chip，这是一个独特的RFID微转带，它能够通过无线电传输其ID 被光激活后的频率。该读数是在基于自定义的基于流体的P-CHIP的分析仪上进行的 同时确定荧​​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）测定资格 以及对绩效的评估和3）使用较大集合 样品。然后将测定结果与样品的PSA分析结果相结合，并用于开发新的 使用多个分析物进行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测试的高灵敏度，以最大程度地减少当前的高假阳性 速度。预计该项目将为社会提供主要的成本和生活方式好处：这种新的多重诊断测定法 因为PCA可以较早地识别需要干预的临床意义的PCA患者，尤其是在结果为 结合常规血清PSA测试。