Tumor-associated carbohydrate antigens: a possible avenue for cancer prevention.
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 ThomsenFriedenreich 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.
Xu
Yanfei
Y
Torrey Pines Institute for Molecular Studies, San Diego, California, USA.
Sette
Alessandro
A
Sidney
John
J
Gendler
Sandra J
SJ
Franco
Alessandra
A
D000483:Alleles; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D005260:Female; D006020:Glycopeptides / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000517:prevention & control*; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006020:Glycopeptides; D015395:Histocompatibility Antigens Class I; D018396:Mucin-1; C016467:Thomsen-Friedenreich antigen