Tumor-Associated Antigens in Early Stage Serous Carcinoma

早期浆液性癌中的肿瘤相关抗原

• 批准号: 7133518
• 负责人: Richard Bruce Roden
• 金额: $ 35.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7133518
• 关键词: antibody; antigens; carcinoma; clinical research; neoplasm /cancer; serum

DESCRIPTION (provided by applicant): Our overall goal is to reduce the morbidity and mortality caused by ovarian serous carcinoma by developing a routine blood screen for earlier detection of incipient disease when current therapies are most effective. Carcinogenesis results in aberrantly expressed and mutated gene products that are potentially antigenic. Such tumor associated antigens (TAAs) and the corresponding immune responses are candidate biomarkers for early stage serous carcinoma. Furthermore, these TAAs may be relevant in the pathogenesis of serous carcinoma and have potential as tumor vaccine antigens. Hypothesis I: Patients generate antibody to TAAs expressed in early stage serous carcinoma. Aim 1: Identify TAAs recognized by sera of patients with early stage serous carcinoma using two complementary technologies; immunoscreening of serous carcinoma cDNA expression libraries (SEREX) and 2D-DIGE/MALDI-TOF of immunoprecipitates from low grade and high grade serous carcinoma. Hypothesis II: Detection of autologous serum antibody to an appropriate panel of TAAs identifies patients with organ-confined and advanced ovarian cancer. Aim 2: Parallel detection of autologous serum antibodies against TAAs of serous carcinoma and, in a large cohort study, to evaluate their predictive value for ovarian cancer. Further we propose to examine the prognostic value and racial differences in antibody to TAAs in sera of serous carcinoma patients. Hypothesis III: Autologous TAAs relevant to ovarian carcinogenesis are expressed by ovarian carcinomas of the same histotype but are absent from, or at a lower level in normal tissue. Aim 3: Determine the expression pattern of TAA panel members in normal and ovarian tumor tissues. We will correlate expression of individual TAAs in tumor tissue with detection of TAA-specific autologous serum antibody. In summary, we propose to develop a highly predictive serum test for early stage serous carcinoma based upon detection of antibody to a panel of ovarian TAAs.

描述（由申请人提供）：我们的总体目标是通过开发常规血液筛查来降低卵巢浆液性癌引起的发病率和死亡率，以便在当前疗法最有效时及早发现初期疾病。致癌作用导致具有潜在抗原性的异常表达和突变的基因产物。这种肿瘤相关抗原（TAA）和相应的免疫反应是早期浆液性癌的候选生物标志物。此外，这些 TAA 可能与浆液性癌的发病机制有关，并具有作为肿瘤疫苗抗原的潜力。假设 I：患者产生针对早期浆液性癌中表达的 TAA 的抗体。目标 1：使用两种互补技术识别早期浆液性癌患者血清所识别的 TAA；对浆液性癌 cDNA 表达文库 (SEREX) 进行免疫筛选，并对低级别和高级别浆液性癌免疫沉淀物进行 2D-DIGE/MALDI-TOF。假设 II：检测针对适当 TAA 组的自体血清抗体可识别患有器官局限性和晚期卵巢癌的患者。目标 2：并行检测针对浆液性癌 TAA 的自体血清抗体，并在大型队列研究中评估其对卵巢癌的预测价值。此外，我们建议检查浆液性癌患者血清中 TAA 抗体的预后价值和种族差异。假设III：与卵巢癌发生相关的自体TAA由相同组织型的卵巢癌表达，但在正常组织中不存在或水平较低。目标 3：确定 TAA 小组成员在正常和卵巢肿瘤组织中的表达模式。我们将肿瘤组织中个体 TAA 的表达与 TAA 特异性自体血清抗体的检测相关联。总之，我们建议根据一组卵巢 TAA 抗体的检测，开发一种针对早期浆液性癌的高度预测性血清检测。