Tumor-Associated Antigens in Early Stage Serous Carcinoma

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，以便在当前治疗最有效时早期检测早期疾病。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）和相应的免疫应答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。假设一：患者产生抗体的TAA表达在早期浆液性癌。目标1：使用两种互补技术鉴定早期浆液性癌患者血清识别的TAA;浆液性癌cDNA表达文库的免疫筛选（SEREX）和来自低级别和高级别浆液性癌的免疫沉淀物的2D-DIGE/MALDI-TOF。假设二：检测一组合适的TAA的自体血清抗体可识别器官局限性和晚期卵巢癌患者。目标二：平行检测浆液性癌TAA的自体血清抗体，并在一项大型队列研究中评估其对卵巢癌的预测价值。此外，我们建议研究浆液性癌患者血清中TAAs抗体的预后价值和种族差异。假设三：与卵巢癌发生相关的自体TAA在相同组织型的卵巢癌中表达，但在正常组织中不表达或表达水平较低。目的3：确定TAA组成员在正常和卵巢肿瘤组织中的表达模式。我们将肿瘤组织中单个TAA的表达与TAA特异性自体血清抗体的检测相关联。总之，我们建议开发一种基于检测卵巢TAAs抗体的早期浆液性癌的高预测性血清试验。

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.