Sialyl-Tn antigen in cancer: from diagnosis to therapy

Sialyl-Tn antigen (STn) is a short O-glycan containing a sialic acid residue a2,6-linked to GalNAcα-O-Ser/Thr. This disaccharide is thought to be biosynthesised by a specific CMP-Neu5Ac: GalNAc a2,6-sialyltransferase termed ST6GalNAc I. ST6GalNAc I compete with O-glycans elongating glycosyltransferases and prevent cancer cells to exhibit longer O-glycans. Several monoclonal antibodies have been raised to detect STn in tissues. While foetal and normal adult tissues weakly express STn, the antigen is over-expressed in a wide range of epithelial cancers and is considered as a good maker of tumour. However, its pattern of expression varies according to the cells morphology and differentiation, which depend on the cancer type. STn seems to be related to invasive behaviour and metastatic potential of the cancer cells, while the involved mechanisms remain unclear. The prognostic value of STn expression has been widely studied, especially in gastric, colorectal, ovarian and breast cancers. For all the cases, the antigen detection is correlated to a decreased survival of the patients. Because of this pan-carcinoma expression associated with an adverse outcome, an anti-cancer vaccine has been designed towards the STn epitope. One thousand of patients with metastatic breast cancers were enrolled in a phase III clinical trial, which has been achieved in mid 2003. The moderated results of this trial enlighten the present limits of the anti-cancer immunotherapy approaches.