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

Recent research strongly suggests a role of plasma-derived anti-P 1 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 P 1 accounts for this discrimination and whether plasma matched ascites samples contain AGA. We also aimed to identify the P 1 antigen in cancer tissue and cultured cells that are recognized by naturally occurring anti-P 1 IgM and to investigate the potential function in respect to cell migration. Our results demonstrated that the IgM to P 1 discriminates patients with ovarian cancer from healthy controls (p=0.0002) and that lower anti-P 1 antibody levels are associated with a slightly higher risk for early relapse. Mass spectrometry identified P 1 and structurally related epitopes in fresh tissue specimens and cultured cells. Ovarian cancer cell line IGROV1 was identified to be P 1 -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-P 1 antibodies from ascites were shown to bind P 1 -expressing cancer cells. IGROV1 was cell-sorted into two subpopulations, P 1 –high (66.1%) and P 1 -low (33.3%) and we found a significantly higher migration rate in P 1 -high expressing cells. Plasma-and ascites-derived natural anti-P 1 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 P 1 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, Andre 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.