Autoantibodies in NSCLC as Markers for Disease

NSCLC 中的自身抗体作为疾病标志物

• 批准号: 6798757
• 负责人: Edward A. Hirschowitz
• 金额: $ 26.22万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-05 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6798757
• 关键词: autoantibody; biomarker; blood tests; clinical research; diagnosis design /evaluation; genetic library; high throughput technology; human genetic material tag; human tissue; immunocytochemistry; immunologic assay /test; microarray technology; neoplasm /cancer diagnosis; nonsmall cell lung cancer; oncoproteins; pathologic process; phage display; polymerase chain reaction; tissue resource /registry

DESCRIPTION (provided by applicant): A variety of diagnostic and therapeutic strategies are being explored to change poor outcomes in lung cancer. Tumor markers, measured in peripheral blood, could complement the evolving clinical approach to lung cancer management. Autoantibodies to tumor-associated proteins may effectively expand the number and range of available serologic markers for lung cancer and be translated into a valuable test for lung cancer. Our preliminary data supports this hypothesis. We used phage-display and biopan techniques to identify multiple autoantibodies to known and unknown tumor-associated proteins in the serum of non-small cell lung cancer (NSCLC) patients. Using conventional immunochemical techniques and novel protein microarray we showed that autoantibodies to individual tumor-associated proteins are found in cancer patient sera and not in normals. Because no single antibody response is likely to be a comprehensive marker, we intend to build on these exciting data and develop an inclusive blood test for lung cancer by profiling sera for a variety of atuoantibodies. We have already identified 21 proteins recognized by autoantibodies in NSCLC patient sera and using these, plus additional proteins identified with these techniques; we will generate a comprehensive a panel of proteins used for antibody measurement. Fluorescent microarray technology, applied generally to gene discovery, is ideal for this purpose. Thus the primary goal of this proposal is to develop a novel blood test for NSCLC. To begin to expand the clinical relevance of this approach, a secondary goal is to show the association of autoantibody responses to tumor protein expression. The data shows feasibility and proof of concept that supports the rationale behind this proposal.

描述(由申请人提供)：正在探索各种诊断和治疗策略来改变肺癌的不良结果。在外周血中测量的肿瘤标志物可以补充不断发展的肺癌治疗临床方法。针对肿瘤相关蛋白的自身抗体可以有效地扩大肺癌可用的血清标志物的数量和范围，并转化为一种有价值的肺癌检测方法。我们的初步数据支持这一假设。我们使用噬菌体展示和生物扫描技术来鉴定非小细胞肺癌(NSCLC)患者血清中针对已知和未知肿瘤相关蛋白的多种自身抗体。利用传统的免疫化学技术和新型的蛋白质芯片，我们发现在癌症患者血清中发现了针对单个肿瘤相关蛋白的自身抗体，而在正常人中没有。因为没有单一的抗体反应可能是一个全面的标志物，我们打算在这些令人兴奋的数据的基础上，通过分析各种抗抗体的血清来开发一种肺癌的包容性血液测试。我们已经在NSCLC患者血清中鉴定了21种被自身抗体识别的蛋白质，并使用这些蛋白质，加上通过这些技术鉴定的其他蛋白质；我们将生成一组全面的蛋白质，用于抗体测量。荧光微阵列技术被广泛应用于基因发现，是实现这一目的的理想选择。因此，这项提议的主要目标是开发一种新的非小细胞肺癌血液检测方法。为了开始扩大这种方法的临床相关性，第二个目标是显示自身抗体反应与肿瘤蛋白表达的关联。数据显示了支持这一提议背后的理由的可行性和概念证明。