Synthetic MUC1 Antitumor Vaccine Candidates with Varied Glycosylation Pattern Bearing R/S-configured Pam3CysSerLys4

The Toll-like receptor 2 ligand Pam(3)CysSer is of particular interest for the construction synthetic vaccines because of its ability to stimulate of the innate immune system. Such vaccines usually comprise Pam(3)CysSer with the natural R-configuration at the glycerol 2-position. Pam(3)CysSer peptide vaccines with natural configuration have been shown to be more efficient than the corresponding R/S diastereomers. In order to clarify whether the effect of the configuration of Pam(3)Cys on the immune response also applies to glycopeptide vaccines, MUC1 glyco-peptide- lipopeptide vaccines bearing either R-or R/S-configured Pam(3)CysSerLys4 were compared for their immunological effects. In order to find out whether glycosylated MUC1 tandem repeat domains comprise not only B-cell epitopes but also T-cell epitopes, two-component vaccines containing the Pam(3)CysSerLys4 lipopeptide and MUC1 glycopeptides with various glycosylation patterns were synthesized, and their immune reactions in mice were studied.