Tumor-Associated Antigens in Early Stage Serous Carcinoma

描述(申请人提供)：我们的总体目标是通过开发一种常规的血液筛查来降低卵巢浆液性癌造成的发病率和死亡率，以便在当前治疗方法最有效的时候早期发现早期疾病。致癌会导致表达异常和突变的潜在抗原性基因产物。这些肿瘤相关抗原(TAA)及其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，并有可能作为肿瘤疫苗抗原。假设I：患者产生早期浆液性癌中表达的抗TAA抗体。目的：利用两种互补技术鉴定早期浆液性癌患者血清识别的TAAs：浆液性癌基因表达文库的免疫筛选和低、高级别浆液性癌免疫沉淀物的2D-DGE/MALDI-TOF。假设II：检测一组合适的TAAs的自体血清抗体可确定器官受限和晚期卵巢癌患者。目的2：平行检测浆液性癌中抗TAA的自身血清抗体，并在一项大型队列研究中评价其对卵巢癌的预测价值。此外，我们建议检测浆液性癌患者血清中抗TAAs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在相同组织类型的卵巢癌中表达，但在正常组织中缺失或表达水平较低。目的：研究TAA组成员在正常卵巢组织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特异性自身血清抗体的检测相关联。综上所述，我们建议开发一种早期浆液性癌的高预测性血清检测方法，其基础是检测一组卵巢TAA的抗体。

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.