N-glycolylneuraminic acid (Neu5Gc)

N-glycolylneuraminic acid (Neu5Gc) is a non-human sialic acid molecule that differs from the human N-acetylneuraminic acid (Neu5Ac) by a single oxygen atom. Humans are genetically unable to synthesize Neu5Gc due to an evolutionary mutation in the CMAH gene, yet it can be metabolically incorporated into human tissues through the consumption of red meat and dairy products. Because it is recognized as foreign by the human immune system, its presence on cell surfaces triggers the production of anti-Neu5Gc antibodies, leading to a state of chronic inflammation known as xenosialitis. In the context of oncology, Neu5Gc is highly expressed on various cancer cells (such as Neu5Gc-GM3 gangliosides), making it a promising tumor-specific neoantigen for targeted immunotherapy. Therapeutic strategies include the development of cancer vaccines like Racotumomab and monoclonal antibodies designed to selectively eliminate Neu5Gc-positive malignant cells while sparing normal human cells that lack the biosynthetic machinery for this glycan.

Other names

NeuGcGycNeuN-glycolyl-neuraminic acid2-keto-3-deoxy-5-glycolylamido-D-glycero-D-galacto-nonulosonic acidHanganutziu-Deicher antigen

Monoclonal antibodies or vaccines targeting Neu5Gc-containing glycans (such as Neu5Gc-GM3) induce antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) against tumor cells expressing the xenoantigen.