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: 7288717
• 负责人: Richard Bruce Roden
• 金额: $ 30.18万
• 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/7288717
• 关键词: Age; Antibodies; Antibody Formation; Antigens; Autologous; Bacteriophages; Benign; Bilateral oophorectomy; Biological Assay; Biological Markers; Blinded; Blood Screening; Blood Tests; CA-125 Antigen; Carcinoma; Cessation of life; Clinical; Cohort Studies; Controlled Study; Data; Depth; Detection; Development; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Disease; Dyes; Early Diagnosis; Early identification; Enrollment; Epithelial; Epithelial ovarian cancer; Exhibits; Expression Library; Genomics; Goals; Histologic; Human; Image Analysis; Immune Sera; Immune response; Immunoglobulin G; Immunohistochemistry; Individual; Invasive; Label; Laboratories; Location; Logistic Regressions; Malignant Neoplasms; Malignant neoplasm of ovary; Minority; Modeling; Molecular Profiling; Morbidity - disease rate; Mutate; Normal tissue morphology; Operative Surgical Procedures; Organ; Outcome; Ovarian; Ovarian Carcinoma; Ovarian Serous Adenocarcinoma; Ovariectomy; Ovary; Pathogenesis; Patients; Pattern; Pelvis; Peptides; Physical Examination; Pilot Projects; Predictive Value; Premalignant; Primary Lesion; Proteins; Proteomics; Publishing; ROC Curve; Rate; Research Personnel; Screening procedure; Sensitivity and Specificity; Serological; Serous; Serum; Specificity; Spottings; Staging; Standards of Weights and Measures; Stream; Symptoms; Technology; Testing; Tissue Microarray; Tumor Antigens; Tumor Cell Derivative Vaccine; Tumor Tissue; Validation; Woman; antigen binding; base; cDNA Expression; carcinogenesis; chemotherapy; cyanine dye 5; member; mortality; mutant; new technology; ovarian neoplasm; peripheral blood; prognostic; programs; racial difference; response; synthetic polymer Bioplex; tumor; uncertain malignant potential neoplasm

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的血液筛选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早期发现初期疾病。致癌作用导致可能具有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理有关，并且具有肿瘤疫苗抗原的潜力。假设I：患者在早期浆液性癌中产生对TAA的抗体。 AIM 1：使用两种补充技术确定早期浆液性癌患者的血清认可的TAA；浆液性癌cDNA表达文库（SEREX）和2D-DIGE/MALDI-TOF的免疫验证来自低级和高级浆液性癌的免疫沉淀物。假设II：检测适当的TAA面板自体血清抗体，可鉴定有器官构成和晚期卵巢癌的患者。 AIM 2：平行检测针对浆液性癌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，我们建议检查浆液性癌患者血清中TAAS抗体的预后价值和种族差异。假设III：与卵巢癌相关的自体TAA由相同组织型的卵巢癌表达，但在正常组织中不存在或较低水平。目标3：确定正常和卵巢肿瘤组织中TAA面板成员的表达模式。我们将将单个TAA在肿瘤组织中的表达与检测到TAA特异性血清抗体的表达。总而言之，我们建议基于检测到卵巢TAA的抗体的检测，为早期浆液性癌开发高度预测性的血清测试。