A+PSA Assay for Improved Prostate Cancer Diagnosis and Risk Assessment

描述（由申请方提供）：针对肿瘤相关抗原（TAA）的循环自身抗体（autoAb）提供了关于宿主免疫活性和内源性肿瘤免疫原性的关键信息。因此，AutoAb在过去一直受到积极的研究。然而，由于缺乏一个敏感的和多重的方法，autoAb仍然难以捉摸的癌症生物标志物。为了避免制备噬菌体展示文库和纯化大量TAA蛋白的要求，我的实验室一直在采取一种有针对性的方法，从TAA中鉴定肽表位，用于定量癌症患者中循环自身抗体。使用前列腺癌作为原型，在先前的R 03资助的支持下，鉴定了来自6种临床相关的前列腺癌相关抗原（PCAA）的表位，即在前列腺癌组织中具有确定表达的PCAA加上在前列腺癌患者中比健康供体显著的自身抗体存在。随后的R21资助帮助将该技术从ELISA转化为多重血清MAP平台，允许在单一反应中同时定量auto-Ab与PSA（一种常规生物标志物）。在实现R21赠款中提出的发展里程碑之后，我们现在寻求R 01的支持，以优化用于临床实验室的所谓“A+PSA”测定（目标1），与更大和更广泛的患者队列进行交叉验证，包括肺癌和结肠癌患者（目标2），并在前列腺癌诊断的背景下前瞻性地和在风险评估的背景下回顾性地验证该测定（目标3）。该项目将使我们能够在未来4年内提供功能齐全的A+PSA检测试剂盒，并在临床试验中对其预期用途进行测试。“A+PSA”检测及其基于逻辑回归的“A+PSA”指数是第一种将免疫系统响应癌症产生的自身抗体与癌症本身产生的常规标志物整合的方法。多功能性、性能和用户友好性使“A+PSA”检测成为临床实验室前列腺癌诊断和/或风险评估的理想选择。A+PSA检测可通过显著降低假阳性率而更好地服务于前列腺癌诊断。它还可以提供风险评估，以区分惰性和侵袭性前列腺癌。

DESCRIPTION (provided by applicant): Circulating autoantibodies (autoAb) against tumor-associated antigens (TAA) provide critical information about the immunocompetence of the host and the immunogenicity of the endogenously arising tumor. AutoAb therefore, have been vigorously investigated in the past. However, due to the lack of a sensitive and multiplex approach, autoAb remain elusive as cancer biomarkers. To circumvent the requirement of preparing phage display libraries and purifying a large panel of TAA proteins, my lab has been taking a targeted approach of identifying peptide epitopes from TAA for quantifying circulating auto-Ab in cancer patients. Using prostate cancer as a prototype, epitopes from 6 clinically relevant prostate cancer-associated antigens (PCAA), i.e. PCAA with defined expressions in prostate cancer tissues plus prominent autoAb presence in prostate cancer patients than healthy donors, were identified with the support of a previous R03 grant. A subsequent R21 grant helped to transform the technology from ELISA to the multiplex seroMAP platform, allowing simultaneous quantification of auto-Ab in conjunction with PSA, a conventional biomarker in a single reaction. Following the achievement of developmental milestones proposed in the R21 grant, we now seek R01 support to optimize the so-called "A+PSA" assay for use in a clinical laboratory (Aim 1), cross-validate with larger and broader patient cohorts including patients with lung cancer and colon cancer (Aim 2), and validate the assay prospectively in the context of prostate cancer diagnosis and retrospectively in the context of risk assessment (Aim 3). This project will allow us to deliver a fully functional A+PSA assay to be tested in its intended use in clinical trials within the next 4 years. The "A+PSA" assay and its logistic regression-based "A+PSA" index, is the first approach that integrates autoAb produced by the immune system in response to cancer with a conventional marker produced by the cancer itself. The versatility, performance power and user-friendliness make "A+PSA" assay ideal for clinical laboratories serving prostate cancer diagnosis and/or risk assessment. The A+PSA assay may better serve prostate cancer diagnosis by significantly reducing false positive rate. It may also provide risk assessment to differentiate between indolent and aggressive prostate cancers.