Resurrecting ancestral sugars: a novel molecular archaeology approach to Prostate cancer immunotherapy

Human cells are coated in a thick layer of sticky sugars called the glycocalyx. Uniquely cancer cells are covered with an excess of the human ‘sialic acid’ sugar Neu5Ac, and this has been shown to camouflage the cells from the immune system. However, 2 million years ago a hydroxylated form of this sugar known as Neu5Gc was also present on human cells, but evolutionary selection drove inactivation of the gene required for conversion of Neu5Ac to Neu5Gc, and this resulted in the loss of the ancestral sugar from the surface of human cells. Following this selection event, humans have developed circulating anti-Neu5Gc IgG antibodies making this sugar antigenic. Our aim is to resurrect this ancestral sugar specifically in prostate cancer cells using antibody-targeted gene delivery. This strategy would aim to unleash the immune system’s existing anti-Neu5Gc antibodies to kill the cancer cells, constituting a completely novel approach to cancer immunotherapy.