Phage Microarray Discovery of New Tumor Autoantibodies

描述（由申请人提供）：前列腺癌的诊断和治疗将大大受益于简单、廉价的血液检查，使临床医生能够更准确地区分侵袭性和非侵袭性肿瘤。该SBIR项目的长期目标是开发一种临床检测方法，用于测量几种前列腺肿瘤相关抗体的血清水平。这些信息，当与更传统的诊断测试相结合时，将有助于医生判断正在发展的肿瘤的转移潜力，从而排除许多不必要的活检。拟议的I期研究旨在建立一种新的噬菌体微阵列技术的概念证明，用于发现疾病早期和晚期患者血清中以前未知的肿瘤相关抗体。DSI的新方法使用了噬菌体展示技术的新应用，不仅可以识别肿瘤特异性自身抗体，还可以识别肿瘤相关抗体，这些抗体在正常血清中天然存在，但随着肿瘤的进展而显着升高。该策略避免了昂贵且耗时的肿瘤抗原纯化，并且使得可以检测与翻译后修饰反应的自身抗体，例如肿瘤相关的糖基化变化。第一阶段的目标集中在实现两个具体目标：1。选择并单独扩增10，000个噬菌体肽克隆，其与来自前列腺癌患者的合并血清中的抗体结合;以及2.将噬菌体克隆整合到微阵列格式中，并筛选来自具有低水平和高水平PSA的患者以及来自健康对照的个体血清样品。在该项目的第二阶段，免疫反应性肽将用于开发一种经济的临床试验，用于分析前列腺肿瘤相关自身抗体的血清水平。这种检测方法有可能成为早期检测前列腺癌的标准诊断程序，并将在全球范围内拥有巨大的市场。

DESCRIPTION (provided by applicant): The diagnosis and treatment of prostate cancer will benefit greatly from the availability of simple, inexpensive blood tests which enable clinicians to distinguish more accurately between aggressive and non aggressive tumors. The long-term goal of this SBIR project is to develop a clinical assay which measures serum levels of several prostate tumor-associated antibodies. This information, when combined with more traditional diagnostic tests, will assist physicians in judging the metastatic potential of a developing tumor and will thus exclude many unnecessary biopsies. The proposed Phase I studies are designed to establish proof of concept of a novel Phage Microarray technology for discovering previously unknown tumor-related antibodies in the sera of patients in the early and later stages of the disease. DSI's new approach uses a novel application of phage display technology to identify not only tumor-specific autoantibodies, but also tumor associated antibodies which are naturally present at low levels in normal sera but are significantly elevated as a tumor progresses. This strategy avoids the costly and time-consuming purification of tumor antigens and makes it possible to detect autoantibodies reactive with post-translational modifications, such as tumor associated changes in glycosylation. The Phase I goals are focused on achieving two Specific Aims:1. Select and individually amplify 10,000 phage peptide clones which bind to antibodies in pooled sera from prostate cancer patients; and 2. Incorporate the phage clones into a microarray format and screen individual serum samples from patients with low and high levels of PSA and from healthy controls. During Phase II of this project, the immunoreactive peptides will be used to develop an economical clinical assay for profiling serum levels of prostate tumor-associated autoantibodies. This assay has the potential to become a standard diagnostic procedure for the early detection of prostate cancer and would have a significant world-wide market.