Sialyl-Tn in Cancer: (How) Did We Miss the Target?

Julien Sylvain , Paula A Videira, Philippe Delannoy

Research output: Contribution to journalArticle

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11 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)435-466
Number of pages32
JournalBiomolecules
Volume2
Issue number4
DOIs
Publication statusPublished - 11 Oct 2012

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Neoplasms
Immunotherapy
Polysaccharides
Sialyltransferases
Carcinoma
Glycosyltransferases
Phase III Clinical Trials
Drug Compounding
Cancer Vaccines
Drug Design
Biosynthesis
N-Acetylneuraminic Acid
Antigens
sialosyl-Tn antigen
Patient Selection
Epitopes
Carrier Proteins
Cells
Carbohydrates
Tissue

Keywords

  • Sialyl-Tn antigen
  • O-glycan
  • ST6GalNAc I
  • Theratope
  • cancer immunotherapy

Cite this

Sylvain , Julien ; Videira, Paula A ; Delannoy, Philippe. / Sialyl-Tn in Cancer: (How) Did We Miss the Target?. In: Biomolecules. 2012 ; Vol. 2, No. 4. pp. 435-466.
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Sialyl-Tn in Cancer: (How) Did We Miss the Target? / Sylvain , Julien; Videira, Paula A; Delannoy, Philippe.

In: Biomolecules, Vol. 2, No. 4, 11.10.2012, p. 435-466.

Research output: Contribution to journalArticle

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