Tumor-Associated Antigens in Early Stage Serous Carcinoma

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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.