Sialyl-Tn antigen (STn) is a short O-
glycan containing a
sialic acid residue a2,6-linked to
GalNAca-O-Ser/Thr. The biosynthesis of STn is mediated by a specific
sialyltransferase termed ST6GalNAc I, which competes with O-
glycans elongating
glycosyltransferases and prevents
cancer cells from exhibiting longer O-
glycans. While weakly expressed by fetal and normal adult tissues, STn is expressed by more than 80% of human
carcinomas and in all cases, STn detection is associated with adverse outcome and decreased overall survival for the patients. Because of its pan-
carcinoma expression associated with an adverse outcome, an anti-
cancer vaccine, named
Theratope, has been designed towards the STn
epitope. In spite of the great enthusiasm around this
immunotherapy,
Theratope failed on Phase III clinical trial. However, in lieu of missing this target, one should consider to revise the
Theratope design and the actual facts. In this review, we highlight the many lessons that can be learned from this failure from the immunological standpoint, as well as from the drug design and formulation and patient selection. Moreover, an irrefutable knowledge is arising from novel
immunotherapies targeting other
carbohydrate antigens and STn
carrier proteins, such as MUC1, that will warrantee the future development of more successful anti-STn
immunotherapy strategies.