Thomsen-Friedenreich Antigen: The 'Hidden' Tumor Antigen

Carbohydrate tumor antigens on glycoproteins and glycolipids are targets for active and passive cancer immunotherapy. These highly abundant antigens are de novo expressed or up-regulated due to changes in the complex glycosylation apparatus of tumor cells, involving sets of enzymes like glycosyltransferases, glycosidases, epimerases, and nucleotide sugar transporters. Various lipid or protein bound carbohydrate tumor antigens are described, for example, GM2, GD2, GD3, fucosylated GM1, Globo H, LeY, Lea, Sialyl-Lea and the mucin core structures Tn, Sialyl-Tn, and the Thomsen-Friedenreich Antigen (TF). Carbohydrate tumor antigens are far more abundant than protein tumor antigens rendering them suitable targets especially for antibodies, for example, highly expressed protein tumor markers as Her-2/neu express about 106 and TF about 107 copies per cell. More recent data show that certain carbohydrate structures are not only targets for humoral but also cellular immune responses.