Xeno-Autoantibodies (327726)

  https://cordis.europa.eu/project/id/327726

  FP7 (2007-2013)

  Immune Recognition of Xeno-Glycans

  Marie Curie Action: "International Incoming Fellowships" (FP7-PEOPLE-2012-IIF)

  nanotechnology  ·  carbohydrates  ·  oncology  ·  immunotherapy  ·  molecular biology

  2013-03-01 Start Date (YY-MM-DD)

  2015-02-28 End Date (YY-MM-DD)

  € 227,231 Total Cost

  Description

‘xeno-autoantibodies’ recognize a dietary immunogenic non-self sugar that is metabolized by cells as self and presented on the cell surface. N-acetylneuraminic acid (Neu5Ac) and its hydroxylated form, N-glycolylneuraminic acid (Neu5Gc) are the two major Sia forms in most mammals. Humans are deficient in the enzyme CMP-Neu5Ac hydroxylase (CMAH) that can synthesize Neu5Gc, however dietary Neu5Gc accumulates in epithelial tumors and become immunogenic. Our previous research recognized dual and opposing roles of IgG isotype xeno-autoantibodies in cancer progression, diagnosis and immunotherapy: they facilitate tumor progression via chronic inflammation at low doses, but mediate tumor inhibition at higher doses in a ‘human-like’ Cmah-/- Neu5Gc-deficient mouse model. Furthermore, we developed a novel sialoglycan microarray that lead to the discovery of a specific xeno-auto-IgG that is novel human serum carcinoma biomarker and potential immunotherapeutic. However, our early studies also revealed that some human sera show high levels of anti-Neu5Gc IgAs that could even be affinity-purified from human serum (7). IgA is the most abundantly produced antibody isotype in the body and the main isotype in mucosal surfaces; It is also present in serum, where IgG is the predominant isotype. I propose a multidisciplinary approach to investigate the biology of IgA xeno-autoantibodies against these unique glycans and their potential involvement in cancer. I will combine glycobiology, immunology, biochemistry, molecular biology, nanotechnology and advanced array techniques to address these lines of investigation both in vitro and in vivo in a relevant mouse model (Cmah-/-).

  Complicit Organisations

1 Israeli organisation participates in Xeno-Autoantibodies.