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

Here we examine the use of glycopeptides containing tumour-associated carbohydrateantigens (TACA) as potential preventive vaccines for carcinomas.Our recent results suggest that CD8+ T cells (CTL) are capableof 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 whenconjugated to designer peptides with optimal binding affinity forclass I MHC molecules. TF- and Tn-specific CTL generated using thisstrategy are capable of recognizing TACA-expressing tumours invitro, suggesting that glycopeptides are as effectively presentedby class I MHC molecules as non-glycosylated peptides. Because theexact sequences of endogenously synthesized glycopeptides are unknown,the TACA-specific T cell repertoire elicited by carbohydrate-basedvaccines is assumed to be degenerate. Here we report that mice geneticallymanipulated to develop TACA-expressing mammary tumours are not tolerantto glycopeptide vaccination. Moreover, we tested the immunogenicityof designer glycopeptides capable of binding multiple HLA allelesas a novel approach for the development of vaccines potentiallyuseful for vaccination of a large fraction of the general population.Our results have suggested that CTL derived from normal donors respondwith high efficiency to glycopeptides in vitro, opening anew avenue for the design of prospective vaccines for cancer prevention.