Abstract POSTER-BIOL-1322: Natural anti-glycan IgM recognize P1 glycosphingolipid expressed on ovarian cancer cells

Abstract

Abstract Recent research strongly suggests a role of plasma-derived anti-P1 antibodies (AGA) in ovarian cancer, as demonstrated by three independent glycan-based immunoassays. The level of these antibodies was lower in ovarian cancer patients and therefore discriminate cancer patients from healthy women. Here we investigate in a separate Australian cohort (n=155) whether IgM or IgG to P1 accounts for this discrimination and whether plasma matched ascites samples contain AGA. We also aimed to identify the P1 antigen in cancer tissue and cultured cells that are recognized by naturally occurring anti-P1 IgM and to investigate the potential function in respect to cell migration. Our results demonstrated that the IgM to P1 discriminates patients with ovarian cancer from healthy controls (p=0.0002) and that lower anti-P1 antibody levels are associated with a slightly higher risk for early relapse. Mass spectrometry identified P1 and structurally related epitopes in fresh tissue specimens and cultured cells. Ovarian cancer cell line IGROV1 was identified to be P1-positive while others (n=7) including human ovarian surface epithelial cells were negative determined by comprehensive flow cytometry. Epitope-mapped and characterized affinity purified anti-P1 antibodies from ascites were shown to bind P1-expressing cancer cells. IGROV1 was cell-sorted into two subpopulations, P1–high (66.1%) and P1-low (33.3%) and we found a significantly higher migration rate in P1-high expressing cells. Plasma-and ascites-derived natural anti-P1 IgM bind to the corresponding selfantigen expressed on the ovarian cancer cell surface. These findings are in concordance with the literature on natural IgM as part of the innate immune system recognizing carbo-neo-epitopes. These results deliver the first evidence that P1 may also be involved in cell migration and therefore may have a role in metastasis. Citation Format: Francis Jacob, Merrina Anugraham, Tatiana Pochechueva, Brian Wan-Chi Tse, Shahidul Alam, Rea Guertler, Nicolai V. Bovin, André Fedier, Neville F. Hacker, Margaret E. Huflejt, Nicolle Packer, Viola A. Heinzelmann-Schwarz. Natural anti-glycan IgM recognize P1 glycosphingolipid expressed on ovarian cancer cells [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1322.