Synthetic Muc1 Based Anticancer Vaccines - 1428 Words

More recently in 2011, Li and coworkers reported fully synthetic MUC1-based anticancer vaccines containing mono-, di- and tetravalent B-cell epitopes conjugated to TLR2 ligand (Figure 1.11).157 The B-cell epitope, MUC1 glycopeptide (HGVTSAPDT*RPAPGS*TAPPA) containing Tn and/or T antigen and TLR2 ligand, Pam3CysSK4 were prepared by solid-phase synthesis. Conjugation of MUC1 glycopeptide epitope and multivalent alkyne-functionalized lipopeptide (TLR2 ligand) was performed by using Cu+ catalyzed click chemistry (Figure 1.11). The tetravalent glycopeptide-lipopeptide candidate bearing the STn-antigen was more immunogenic compared to its monovalent and divalent counterparts and the tetravalent candidate (Figure 1.11c ) was able to initiate CDC-mediated killing of tumor cells.158 Figure 1.11. Structural representation of multivalent MUC1 glycopeptide conjugates with the TLR 2 ligand. Another two-component therapeutic glycopeptide vaccine developed by Dr. Li’s group contained the MUC1 tandem repeat sequence covalently attached to BSA or different tetanus toxoid derived T-cell peptide epitopes.159 In this study, the MUC1 tandem repeat glycopeptide sequence HGVTSAPDTRPAPGSTAPPA that was decorated with various combination of T-,Tn- and STn-antigen, was coupled to three different universal T-helper cell epitope peptides, P2 ( TT830–843- QYIKANSKFIGITE), P4 (TT1273–1284- GQIGNDPNRDIL), and P30 (TT947–967-FNNFTVSFWLRVPKVSASHLE) and to BSA (Figure 1.12). It was found that the vaccine