Glycans at the forefront of cells facilitate immune recognition processes.
Cancer cells commonly present altered cell surface glycosylation, especially manifested in the expression of
sialic acid at the termini of
glycolipids and
glycoproteins. Although
tumor-associated carbohydrate antigens (TACAs) result in expression of altered-self, most such
carbohydrates do not elicit strong humoral responses. Various strategies had been devised to elicit increased immunogenicity of such TACA aiming for potent immunotherapeutic
antibodies or
cancer vaccines. However some
carbohydrates are immunogenic in humans and hold potential for novel glycotherapies.
N-Glycolylneuraminic acid (Neu5Gc) is a foreign immunogenic
sugar in humans originating from the diet (e.g., red meat) and subsequently expressed on the cell surface, especially accumulating on
carcinoma. Consequently, the human immune system detects this non-self
carbohydrate generating a broad anti-Neu5Gc antibody response. The co-existence of Neu5Gc/anti-Neu5Gc within humans spurs chronic
inflammation mediated disease, including
cancer. Concurrently, anti-Neu5Gc
antibodies hold potential for novel targeted
therapy. αGal is another foreign immunogenic
carbohydrate antigen in humans and all humans have circulating anti-Gal
antibodies. This review aims to describe the immunogenicity of Neu5Gc and its implications for human diseases, highlighting differences and similarities with αGal and its potential for novel targeted
theranostics.