Synthetic Multivalent Glycopeptide-Lipopeptide Antitumor Vaccines: Impact of the Cluster Effect on the Killing of Tumor Cells

Multivalent synthetic vaccines were obtained by solid‐phase synthesis of tumor‐associated MUC1 glycopeptide antigens and their coupling to a Pam3Cys lipopeptide through click reactions. These vaccines elicited immune responses in mice without the use of any external adjuvant. The vaccine containing four copies of a MUC1 sialyl‐TN antigen showed a significant cluster effect. It induced in mice prevailing IgG2a antibodies, which bind to MCF‐7 breast tumor cells and initiate the killing of these tumor cells by activation of the complement‐dependent cytotoxicity complex. Multivalent vaccines containing a MUC1 glycopeptide bearing the STn antigen were chemically synthesized and immunologically evaluated. The induced immune responses in mice were dependent on the valence of the glycopeptide. The antisera exhibited strong binding to tumor cells which resulted in tumor cell death. This novel effect of clustered multivalent vaccines can be attributed to the altered pattern of the induced antibody isotypes.