Abstract 2220: Autoantibody detection of high-grade serous ovarian cancer with paraneoplastic antigens

Abstract

Abstract Improved early detection methods for ovarian cancer are necessary as the majority of cases present at late stage metastatic disease with a poor prognosis. Early stages of tumor development initiate an immune response, eliciting antibodies that target tumor associated antigens. Paraneoplastic neurological syndromes are rare autoimmune disorders that develop when the unregulated immune response against a tumor also targets healthy cells, due to shared tumor antigen expression with nervous system and muscle tissue. As these syndromes generally precede detection of a tumor, paraneoplastic antibodies are previously unexplored candidate biomarkers for early diagnosis of ovarian cancer. We have detected paraneoplastic antibodies in serum samples from patients with high-grade serous ovarian cancer (HGSOC) that did not present with paraneoplastic neurological syndrome symptoms using paraneoplastic diagnostic line blots. Ovarian cancer specific epitopes discovered previously in our laboratory by phage-display biopanning were evaluated for both homology to paraneoplastic antigens and for reactivity with paraneoplastic neurological syndrome patient sera. Western blot screening revealed a panel of paraneoplastic antigens that distinguished HGSOC patient sera autoantibody reactivity from healthy and benign sera. An indirect ELISA for measuring patient serum autoantibody reactivity was developed and correlated with western blot results. A panel consisting of 8 antigens: 5 paraneoplastic antigens, 2 well-characterized tumor associated antigens, and a non-reactive control was selected for screening on ELISA against patient serum samples representing each group of HGSOC early stage, HGSOC late stage, healthy, and benign. Biomarkers identified can contribute to an autoantibody diagnostic panel for early clinical diagnosis of ovarian cancer, which would allow for timely therapeutic intervention with potential to improve patient outcome. Citation Format: Laura C. Hurley, Nancy K. Levin, Madhumita Chatterjee, Michael A. Tainsky. Autoantibody detection of high-grade serous ovarian cancer with paraneoplastic antigens [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2220.