All living cells are covered with a characteristic sugar-coat unique for each organism and that is often altered in cancer. This result in cell surface presentation of unique tumor-associated carbohydrate antigens, many of which involve aberrant expression of Sialic acids. Sialic acids (Sia) are 9-carbon backbone acidic sugars found at the tips of various glycoproteins and glycolipids. The two common Sias in most mammals are N-acetylneuraminic acid (Neu5Ac) and its hydroxylated counterpart N-glycolylneuraminic acid (Neu5Gc), which differ by one oxygen atom. Humans are genetically deficient in Neu5Gc synthesis, yet it metabolically incorporates into human cells from dietary sources, especially accumulating on carcinomas. This result in replacement of Neu5Ac with Neu5Gc at the tips of cell surface carbohydrate chains leading to expression of neo-tumor associated carbohydrate antigens. Neu5Gc-containing tumor-associated carbohydrate antigens are immunogenic in humans and it was shown that polyclonal anti-Neu5Gc IgGs hold immunotherapeutic potential both in vitro and in vivo. We generated nano-ghost cell mimetics as novel glyco-nanoparticle (GNP) immunogens presenting Neu5Gc in its natural context. We then immunized Cmah-KO mice with Neu5Gc-GNP as a potential active cancer vaccine against various Neu5Gc-containing tumor-associated carbohydrate antigens. Using glycan microarray analysis we show the Neu5Gc-GNP immunization result in a robust and diverse anti-Neu5Gc antibodies response with evident cancer therapeutic potential. These antibodies could also recognize immunogenic Neu5Gc-containing antigens on commercial bioprosthetic heart valves made of non-human mammalian cardiac tissues. Their potential role in bioprosthetic valve deterioration in human patients is further investigated.

Targeting sugar antigens in cancer and heart diseases with glyco-nanoparticle

251st National Meeting (2016)

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