Tumor-associated carbohydrate antigens: A possible avenue for cancer prevention

Yanfei Xu, Alessandro Sette, John Sidney, Sandra J. Gendler, Alessandra Franco

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Here we examine the use of glycopeptides containing tumour-associated carbohydrate antigens (TACA) as potential preventive vaccines for carcinomas. Our recent results suggest that CD8+ T cells (CTL) are capable of recognizing TACA in a conventional class I MHC-restricted fashion. The Thomsen-Friedenreich antigen (TF), a disaccharide, and Tn, its immediate precursor, are TACA largely expressed in carcinomas. TF and Tn can be successfully used as Th-independent vaccines when conjugated to designer peptides with optimal binding affinity for class I MHC molecules. TF- and Tn-specific CTL generated using this strategy are capable of recognizing TACA-expressing tumours in vitro, suggesting that glycopeptides are as effectively presented by class I MHC molecules as non-glycosylated peptides. Because the exact sequences of endogenously synthesized glycopeptides are unknown, the TACA-specific T cell repertoire elicited by carbohydrate-based vaccines is assumed to be degenerate. Here we report that mice genetically manipulated to develop TACA-expressing mammary tumours are not tolerant to glycopeptide vaccination. Moreover, we tested the immunogenicity of designer glycopeptides capable of binding multiple HLA alleles as a novel approach for the development of vaccines potentially useful for vaccination of a large fraction of the general population. Our results have suggested that CTL derived from normal donors respond with high efficiency to glycopeptides in vitro, opening a new avenue for the design of prospective vaccines for cancer prevention.

Original languageEnglish (US)
Pages (from-to)440-448
Number of pages9
JournalImmunology and Cell Biology
Volume83
Issue number4
DOIs
StatePublished - Aug 1 2005

Keywords

  • Glycopeptide
  • Immunotherapy
  • TACA
  • Tn

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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