AUTOLOGOUS ANTIBODY FOR OVARIAN CANCER SCREENING

描述：(申请人提供)我们的总体目标是减少 发展血常规引起卵巢癌的发病率和死亡率 现有治疗方法筛查早期卵巢癌 是最有效的。本申请中描述的研究响应于 NCI报告《卵巢癌的新方向》中的建议。在 在本提案的背景下，卵巢癌是指源于 世界卫生组织中的表面上皮，即所谓的“表面上皮-基质” 组织的分类。卵巢癌是所有癌症中最致命的。 妇科恶性肿瘤，因为大多数女性都患有播散性疾病 这很少通过目前的治疗方法治愈。相反，原发肿瘤局限于 卵巢癌(I期)治疗相当成功。因此，及早发现 卵巢癌的风险是至关重要的。不幸的是早期诊断 卵巢癌的并发症是卵巢不能直接进入 检查时，缺乏症状和缺乏足够的敏感性和 特异性筛查试验。 与癌变相关的分子变化诱导基因突变 表达和/或产生潜在的突变基因产物 抗原性。我们已经证明卵巢癌患者会产生 针对这种肿瘤抗原的自体抗体，并利用这些 用于肿瘤抗原表达克隆的抗体。这种技术被称为 SEREX是强大的，因为它识别了两种类型的潜在生物标记物； SEREX抗原本身和针对该病毒的自身抗体反应 SEREX抗原。抗肿瘤抗原的自体抗体可能在 早期卵巢癌患者的外周血样本，以及 因此代表着很有前途的生物标志物。我们假设检测到的 与适当的SEREX抗原反应的自体血清抗体识别 有癌前病变或癌变的患者。因此，具体目标1是 抗上皮性浆膜抗原自身血清抗体的检测 用酶联免疫吸附试验(ELISA)检测卵巢癌 病例/对照研究，评价其在卵巢检测中的预测价值 癌症。将每个标记的预测值与CA125的预测值进行比较， 是目前唯一被批准的卵巢癌生物标记物。血清生物标志物 对I期卵巢癌具有良好特异性和敏感性的检测方法 将被开发用于快速临床应用。

DESCRIPTION: (provided by applicant) Our overall goal is to reduce the morbidity and mortality caused by ovarian cancer by developing a routine blood screen for earlier detection of incipient ovarian cancer when current therapies are most effective. The research described in this application is responsive to recommendations in the NCI report "New Directions in Ovarian Cancer." In the context of this proposal, ovarian cancer refers to tumors derived from the surface epithelium, so-called 'surface epithelial-stromal' in the World Health Organization's classification. Ovarian cancer is the most lethal of all gynecologic malignancies because most women present with disseminated disease that is rarely cured by current therapies. Conversely, primary tumor confined to the ovary (stage I) is treated quite successfully. Therefore early detection of ovarian cancer is critical. Unfortunately the diagnosis of early stage ovarian cancer is complicated by inaccessibility of the ovaries to direct examination, a lack of symptoms and absence of a sufficiently sensitive and specific screening test. The molecular changes associated with carcinogenesis induce aberrant gene expression and/or generate mutated gene products that are potentially antigenic. We have demonstrated that ovarian cancer patients generate autologous antibodies against such tumor antigens, and exploited these antibodies for expression cloning of tumor antigens. This technique, termed SEREX, is powerful because it identifies two types of potential biomarker; the SEREX antigen itself and the autologous antibody response specific for the SEREX antigen. Autologous antibodies to tumor antigens may be detectable in peripheral blood samples of patients with early stage ovarian cancer, and therefore represent promising biomarkers. We hypothesize that detection of autologous serum antibody reactive with appropriate SEREX antigens identifies patients with pre -cancerous or cancerous lesions. Therefore, Specific Aim 1 is to detect autologous serum antibodies against SEREX antigens of epithelial ovarian cancer by enzyme-linked immunosorbant assay (ELISA) and, in a case/control study, to evaluate their predictive value for detecting ovarian cancer. The predictive value of each marker will be compared to that of CA125, the only currently approved biomarker for ovarian cancer. Serum biomarker assays with promising specificity and sensitivity for stage I ovarian cancer will be developed for rapid clinical application.