Cel
‘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-/-).
Dziedzina nauki
Zaproszenie do składania wniosków
FP7-PEOPLE-2012-IIF
Zobacz inne projekty w ramach tego zaproszenia
System finansowania
MC-IIF - International Incoming Fellowships (IIF)Koordynator
69978 Tel Aviv
Izrael