Phage Microarray Discovery of New Tumor Autoantibodies

描述(申请人提供)：前列腺癌的诊断和治疗将大大受益于简单、廉价的血液测试的可用性，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癌相关抗体的血清水平。这些信息与更传统的诊断测试相结合，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组织检查。拟议的第一阶段研究旨在建立一种新的噬菌体微阵列技术的概念证明，该技术用于在疾病早期和晚期患者的血清中发现以前未知的肿瘤相关抗体。DSI的新方法使用噬菌体展示技术的一种新应用，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，这些抗体自然存在于正常血清中，但随着肿瘤的进展而显著升高。这种策略避免了昂贵和耗时的肿瘤抗原纯化，并使检测与翻译后修饰反应的自身抗体成为可能，例如肿瘤相关的糖基化变化。第一阶段的目标集中于实现两个具体目标：1.选择并单独扩增10,000个与前列腺癌患者混合血清中的抗体结合的噬菌体多肽克隆；2.将这些噬菌体克隆合并到微阵列格式中，并筛选来自PSA水平低和高水平的患者以及健康对照组的单个血清样本。在这个项目的第二阶段，免疫活性多肽将被用来开发一种经济的临床检测方法，用于分析前列腺癌相关自身抗体的血清水平。这项检测有可能成为前列腺癌早期检测的标准诊断程序，并将在全球拥有重要的市场。

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.