XENO-AUTOANTIBODIES
Immune Recognition of Xeno-Glycans
| Coordinatore | TEL AVIV UNIVERSITY
Organization address
address: RAMAT AVIV contact info |
| Nazionalità Coordinatore | Israel [IL] |
| Totale costo | 227˙231 € |
| EC contributo | 227˙231 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2012-IIF |
| Funding Scheme | MC-IIF |
| Anno di inizio | 2013 |
| Periodo (anno-mese-giorno) | 2013-03-01 - 2015-02-28 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
TEL AVIV UNIVERSITY
Organization address
address: RAMAT AVIV contact info |
IL (TEL AVIV) | coordinator | 227˙231.20 |
Mappa
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Obiettivo del progetto (Objective)
'‘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-/-).'