The unexpected production of the Forssman antigen in cancer cells opens new anticancer perspectives

Researchers from the Yamamoto lab at the Josep Carreras Leukaemia Research Institute have found that mutations at the human blood group A transferase (hAT) protein in cancer cells can turn it into a Forssman synthase. Cancer cells with this alteration produce and display the rare Forssman antigen on its membranes, a feature that could be targeted very efficiently using immunotherapy.

The unexpected production of the Forssman antigen in cancer cells opens new anticancer perspectives
The unexpected production of the Forssman antigen in cancer cells opens new anticancer perspectives

Most of us are aware of our blood type (A+, AB-, O+, etc.) and the impact it has on, for instance, blood transfusion compatibility. Molecularly, some blood types, such as ABO, refer to a distinct pattern of modifications added to the membrane lipids and proteins in many of our cells. These modifications are made of a string of sugars and are specific for each species, being used as evolutionary barriers avoiding cross breeding during natural history.

The Immunohematology and glycobiology group of the Josep Carreras Leukaemia Research Institute, led by Dr. Fumiichiro Yamamoto, has been studying blood types and their aberrations in cancer cells for a long time. As it is widely known, cancer cells accumulate many genetic alterations and, sometimes, these affect the blood type machinery, creating an aberrant pattern of modifications in the cell’s membrane that could be exploited therapeutically.

In a recent publication at the specialized journal Scientific Reports (Nature publishing group), the team, spearheaded by postdoctoral researcher Dr. Emili Cid, describes how some mutations at the protein responsible for the synthesis of the A antigen, the hAT protein, can also produce the Forssman antigen, a feature seldomly found in human cells (but commonly present in other mammals like dogs and rats).

The research demonstrates that slight alterations in the stem region of hAT, an unstructured zone used as an extension to reach the top of the membrane proteins it modifies, can turn this otherwise boring part of the protein into a functional Forssman synthase. As striking as it can be, the evidence is sound and cells with those alterations show the presence of Forssman antigen on its membrane lipids unambiguously.

This finding is good news for cancer therapy since the new wave of super-specific immune-based drugs relies on the identification of features highly specific for cancer cells. The more specific, the less secondary effects. The fact that the Forssman antigen is absent in the vast majority of humans makes it a perfect candidate.

Estimations pointed that the Forssman antigen could be present in around 20% of tumors, especially in patients suffering from gastrointestinal, pancreatic and prostate cancer (epithelial origin). These figures come from old reports and must be updated using modern techniques but, if confirmed, the Forssman antigen could be a successful target to fight solid and hematological cancers in the future.