Epitope Array to Complement PSA Tests for Early Detection of Prostate Cancer

描述(由申请人提供)： 最近，检测患者血清中抗前列腺癌相关抗原(PCAA)的自体抗体(Ab)再次受到重视，以此来克服PSA检测早期检测缺乏特异性的问题。然而，为了建立针对PCAA的体液反应作为诊断工具，需要一大批临床相关的PCAA。大规模纯化PCAA的单个重组蛋白是不可行的。为了绕过这一障碍，我们使用计算机辅助算法来预测原型PCAA的B细胞表位，如NY-ESO-1和XAGE-1b。这些PCAA的B细胞表位可以被快速识别并用于检测抗体反应，其频率和敏感性与全长重组蛋白相似。我们假设，来自临床相关PCAA的B细胞表位可以被汇编为表位阵列，用于补充血清PSA检测，以早期检测前列腺癌及其复发。为了验证这一假设，并建立前列腺癌表位阵列技术，我们提出了以下具体目标：1)。从一组临床相关的PCAA中识别线性B细胞表位，这些表位预计覆盖95%的已知前列腺癌患者，特异性超过85%。2)。目的：评价表位阵列在前列腺癌回顾性检测中的敏感性和特异性。表位阵列的诊断潜力将与46例PSA水平低至中等的前列腺癌患者的PSA测试进行比较。我们还将测试表位阵列是否为检测前列腺癌的PSA测试增加了额外的力量。这项研究将提供针对临床相关PCAA的表位阵列是检测前列腺癌的可行方法的原则证据。这项新技术可能会补充PSA检测，以早期发现前列腺癌及其未来的复发。

DESCRIPTION (provided by applicant): Recently, detection of autologous antibodies (Ab) in patients' sera against individual prostate cancer- associated antigens (PCAA) received renewed attention as a means to overcome the lack of specificity of the PSA test for early detection. However, to establish humoral responses against PCAA as a diagnostic tool, a large panel of clinically relevant PCAA is required. Purifying individual recombinant proteins of PCAA is not practical on large scales. To circumvent this obstacle, we used computer-assisted algorithms to predict B cell epitopes from prototypic PCAA, such as NY-ESO-1 and XAGE-1b. B cell epitopes from these PCAA can be rapidly identified and used for detection of antibody responses with similar frequencies and sensitivities as the full-length recombinant proteins. We hypothesize that B cell epitopes from clinically relevant PCAA can be compiled as an epitope array that will complement serum PSA tests for the early detection of prostate cancer and its recurrence. To test this hypothesis and to establish the epitope array technology for prostate cancer, we propose the following specific aims: 1). To identify linear B cell epitopes from a panel of clinically relevant PCAA, which are predicted to cover 95% of known prostate cancer patients with more than 85% specificities. 2). To assess the sensitivity and specificity for the retrospective detection of prostate cancer by epitope arrays. The diagnostic potential of epitope arrays will be compared with PSA tests in 46 prostate cancer patients with low to intermediate PSA levels. We will also test whether epitope arrays add additional power to PSA tests for detecting prostate cancer. This investigation will provide proof of principle that epitope arrays against clinically relevant PCAA are feasible approaches for detection of prostate cancer. This novel technology may complement PSA test for early detection of prostate cancer and its recurrence in the future.