Serologic analysis of ovarian tumor antigens reveals a bias toward antigens encoded on 17q

Abstract

We utilized SEREX immunoscreening to identify a set of novel tumor antigens that are associated with human serous ovarian cancer and may prove useful for the early detection and treatment of this disease. Extensive screening with a panel of sera from 25 late-stage ovarian cancer patients against 3 independent cDNA libraries identified a set of 9 antigens that were immunogenic in more than 1 patient and not in a panel of 20 -45 normal female serum donors. These antigens include p53, NY-ESO-1, UBQLN1, HOXB6, TOP2A, putative helicase-RUVBL (RUVBL), HMBA-inducible (HEXIM1), DDX5 and HDCMA. Ten of 25 ovarian cancer patients (40%) expressed serum IgG to at least 1 of these antigens, while 14% (4/25) had antibodies to 2 or more antigens. Unexpectedly, 4 antigens identified in this screen, DDX5, HEXIM1, TOP2A and HOXB6, are encoded within a region of 17q that also includes the genes for HER2/neu, Homeobox-B7 and BRCA1. Real-time RT-PCR analysis showed that mRNA for HER2/neu and 3 SEREX-defined antigens, TOP2A, HOXB6 and DDX5, was more abundant in ovarian tumors than most normal tissues, including normal and benign ovarian tissues, suggesting that elevated expression of genes encoded within this region of chromosome 17 is a common event in ovarian tumors. Thus, these abnormal expression patterns combined with the endogenous immune response suggests that these antigens represent potential targets for immunotherapy.

Dominant B cell epitope from NY‐ESO‐1 recognized by sera from a wide spectrum of cancer patients: Implications as a potential biomarker

“…21,22 In order to exploit Ab responses against SEREX-defined TAA as potential biomarkers for cancer detection, prognosis and prediction, we need a large panel of TAA that covers a broad range of patients with a particular type of cancer.…”

“…22 The former approach requires large amounts of sera individually pre-adsorbed with E. coli phage lysates for the purpose of reduction of background; the latter is a robust method to screen relatively large numbers of patients' sera. In most recent studies, the feasibility to detect Ab using an array of purified recombinant proteins has been demonstrated.…”

“…In most recent studies, the feasibility to detect Ab using an array of purified recombinant proteins has been demonstrated. [21][22][23] However, to investigate a large panel of TAA that covers a broad range of patients with a certain cancer requires the purification of individual TAA protein, which is often difficult to achieve. Previous studies even showed that many of the SEREX-defined TAAs such as TOP2A, DDX5 and HOXB6 were difficult to express as recombinant proteins.…”

“…Previous studies even showed that many of the SEREX-defined TAAs such as TOP2A, DDX5 and HOXB6 were difficult to express as recombinant proteins. 22 To circumvent the requirement of purifying individual TAA protein, we propose identifying dominant B-cell epitopes for measuring Ab responses against TAA.…”

Tumor-associated Antigen Arrays for the Serological Diagnosis of Cancer

“…A later variant of this approach, termed SEREX, used cDNA expression libraries that were constructed from a patient's tumors and screened with autologous sera (117,118). SEREX has been exploited by several groups for the identification of hundreds of candidate TAAs in various human cancer types (119), including but not limited to lung cancer (28), liver cancer (120), breast cancer (121), prostate cancer (122), ovarian cancer (123), renal cancer (124), head and neck cancer (125), esophageal cancer (126), lymphoma (127), and leukemia (89). Although a powerful approach for the identification of candidate TAAs, SEREX has several limitations.…”