Self-adjuvanting synthetic antitumor vaccines from MUC1 glycopeptides conjugated to T-cell epitopes from tetanus toxoid.

The T-helper epitope peptide P30 (green in the scheme) from tetanus toxoid was used as the immunostimulant in MUC1 glycopeptide antitumor vaccines and apparently also acts as a built-in adjuvant. P30-conjugated glycopeptide vaccines containing three glycans in the immunodominant motifs PDTRP and GSTAP induced much stronger immune responses and complement dependent cytotoxicity mediated killing of tumor cells when applied in plain PBS solution without complete Freund's adjuvant.

Multivalente synthetische Glycopeptid-Lipopeptid-Antitumorvakzine: Auswirkung des Cluster-Effekts auf das Abtöten von Tumorzellen

Multivalente synthetische Vakzine wurden durch Festphasensynthese von tumorassoziierten MUC1-Glycopeptidantigenen und deren Kupplung an ein Pam3Cys-Lipopeptid durch Klick-Reaktion gewonnen. Diese Vakzine losen in Mausen Immunreaktionen aus, ohne dass externe Adjuvantien angewendet werden. Die vier MUC1-Sialyl-TN-Antigene enthaltende Vakzine zeigte einen signifikanten Cluster-Effekt. Sie induzierte in Mausen vorwiegend IgG2a-Antikorper, die an MCF-7-Brusttumorzellen binden und diese Tumorzellen durch Aktivierung des Complement-abhangigen Cytotoxizitatskomplexes (CDC) abtoten.

MUC1-Glycopeptidkonjugate mit T-Zellepitopen von Tetanus-Toxoid als vollsynthetische Antitumor-Vakzine mit Eigenverstärkungseffekt

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 Pam3 Cys 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.