| Autoimmunity is now emerging as a promising strategy for cancer therapy. Through the combination of antigens on the cell surface and antibodies exist in human serum we can kill the target cells without physical and chemical treatments which are toxic to cells.Glycosylation is an important post translational modification which can be chosen as the therapeutic agents for tumor immunotherapies. A large set of carbohydrate antigens have been found in human serum,such as anti-α-Gal, anti-Rhamnose、 anti-Forssman (GalNAc α 1-3GalNAcP)、anti-Mamnose、anti-GalNAc,etc.Among them researches on anti-α-Gal and anti-Rhamnose are hot research fields in recent years,most of which are target on some diseases especially on tumor immunotherapies.Since the metabolic oligosaccharide engineering has been a mature technology capable of modifying cell surface sugars in living cells, we introduce azido, a biorthogonal functional group onto the cell surface and using "click chemistry", the reaction between azido and alkyne, to modify the cell surface.Since sialic acid biosynthetic pathway is permissive of non-natural analogues of N-acetylmannosamine (ManNAc) according to other literatures. Azides can be introduced into cell surface glycoconjugates by metabolism of a synthetic azidosugar through sialic acid biosynthetic pathway. We use N-ManNAz, an analogue of ManNAc, as metabolic precursor to modify cell surface with azido and then react with alkynyl compound containing Rha antigen to introduce Rha into tumor cell surface. Because of the existance of abundant natural Rha antibody in human serum, which can recognize the Rha epitope occurring on the cell surface and finally be destroyed by human immune system through complement-dependent cytotoxicity (in vitro and in vivo) or antibody-dependent cell-mediated cytotoxicity(in vivo). In this process we used the method of metabolic engineering, bioorthogonal chemistry and immunology that provided a new strategy for cancer treatment. |
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