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Sialyl-Tn in Cancer: (How) Did We Miss the Target?
Structural and Functional Glycobiology Unit, UMR CNRS 8576, University of Sciences and Technologies of Lille, 59655 Villeneuve d’Ascq, France
CEDOC, Departamento de Imunologia, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal
* Author to whom correspondence should be addressed.
Received: 29 August 2012; in revised form: 27 September 2012 / Accepted: 30 September 2012 / Published: 11 October 2012
Abstract: 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.
Keywords: Sialyl-Tn antigen; O-glycan; ST6GalNAc I; Theratope; cancer immunotherapy
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Julien, S.; Videira, P.A.; Delannoy, P. Sialyl-Tn in Cancer: (How) Did We Miss the Target? Biomolecules 2012, 2, 435-466.
Julien S, Videira PA, Delannoy P. Sialyl-Tn in Cancer: (How) Did We Miss the Target? Biomolecules. 2012; 2(4):435-466.
Julien, Sylvain; Videira, Paula A.; Delannoy, Philippe. 2012. "Sialyl-Tn in Cancer: (How) Did We Miss the Target?" Biomolecules 2, no. 4: 435-466.