Peptide Array for Profiling of Autoantibodies in Non-small Cell Lung Cancer

描述(由申请人提供)：美国每年约有135,000例新诊断的非小细胞肺癌(NSCLC)病例，但其中只有20%-25%的患者会在足够早的阶段被诊断出来，可以通过手术或其他程序治愈。当与放射成像结合使用时，对非小细胞肺癌的灵敏和特异的血液检测可能是一种具有临床价值和成本效益的早期诊断工具。免疫系统在肿瘤转移发生之前很久就会通过分泌自身抗体来对肿瘤相关蛋白做出反应。对外周血中这一重要的循环肿瘤标记物进行自身抗体谱分析，可以帮助我们识别合适的靶标多肽。我们已经开发了一组21个短肽，它们被形成为蛋白质微阵列，用于简单的捕获免疫分析。当用血液样本进行探测时，该阵列可以识别非小细胞肺癌中肿瘤相关抗体的存在，但在疾病早期和晚期，其敏感度和特异度均超过90%，而在正常人中则不存在。由于用于测量一组癌症患者和风险匹配对照的血清中的肿瘤相关抗体，该测试提供的预测准确性超过了目前可用的循环NSCLC相关蛋白标记物。这项应用的总体目的是准备一组多肽靶标的微阵列，并证明它们能够测量自身抗体谱，以前所未有的灵敏度和特异性将癌症与正常血液样本区分开来。纯化多肽的微阵列将用于严格优化和标准化多靶点免疫分析的所有技术和临床性能指标。我们最初的临床应用将是肺癌的早期发现，尽管在肺癌治疗中的多种应用是合理的。我们的数据显示了可行性和概念证明，支持进一步开发和测试这一方法的基本原理。随后的第二阶段应用将导致使用适当的平台进行最终标记验证试验，以应用于非小细胞肺癌的临床筛查。因此，这项应用的主要目标是开发一种新的非小细胞肺癌血液检测方法，可以迅速转化为临床实践。早期发现肺癌的血液测试可以提供一种成本效益高的筛查方法，与CT扫描相结合将使降低肺癌严重死亡率的可行策略成为可能。

DESCRIPTION (provided by applicant): Approximately 135,000 new cases of non-small cell lung cancer (NSCLC) are diagnosed each year in the USA, yet only 20%-25% of those patients will be diagnosed at a sufficiently early stage to be cured by surgical or other procedures. When used in concert with radiographic imaging, a sensitive and specific blood test for NSCLC could be a clinically valuable and cost-effective tool for early diagnosis. The immune system responds to tumor-associated protein by secreting autoantibodies long before metastasis occurs. Autoantibody profiling for this important group of circulating tumor markers in peripheral blood has lead us to the identification of appropriate target peptides. We have developed a panel of 21 short peptides which were formatted as a protein microarray for use in a simple capture immunoassay. When probed with a blood sample the array can identify the presence of tumor-associated antibodies in NSCLC but not in normals with both sensitivity and a specificity exceeding 90% at early and later stages of the disease. As used to measure tumor-associated antibodies in serum from a cohort of cancer patients and risk-matched controls, this test affords predictive accuracy that exceeds that of currently available circulating NSCLC- associated protein markers. The overall purpose of this application is to prepare microarrays of a panel of peptide targets and to demonstrate that they enable measurement of autoantibody profiles that can distinguish cancer from normal blood samples with unprecedented sensitivity and specificity. Microarrays of the purified peptides will be used for rigorous optimization and standardization of all technical and clinical performance measures for the multi-target immunoassay. Our initial clinical application will be early detection of lung cancer, although multiple applications in lung cancer management are rational. Our data shows feasibility and proof of concept that supports the rationale for further development and testing of this approach. A subsequent Phase II application will lead to use of an appropriate platform for definitive marker validation trials for application to clinical screening of NSCLC. Thus the primary goal of this application is to develop a novel blood test for NSCLC that can be rapidly translated into clinical practice. A blood test for early detection of lung cancer could provide a cost-effective screening approach, and in concert with CT scanning would enable a viable strategy for reducing the severe mortality rate of this disease.