Synthetic MUC1 Antitumor Vaccine with Incorporated 2,3‐Sialyl‐T Carbohydrate Antigen Inducing Strong Immune Responses with Isotype Specificity |
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Authors: | David Straßburger Markus Glaffig Natascha Stergiou Sabrina Bialas Prof. Dr. Pol Besenius Prof. Dr. Edgar Schmitt Prof. Dr. Horst Kunz |
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Affiliation: | 1. Institut für Organische Chemie, Johannes Gutenberg–Universit?t Mainz, Mainz, Germany;2. Institut für Immunologie, Johannes Gutenberg-Universit?t Mainz, Mainz, Germany |
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Abstract: | The endothelial glycoprotein MUC1 is known to underlie alterations in cancer by means of aberrant glycosylation accompanied by changes in morphology. The heavily shortened glycans induce a collapse of the peptide backbone and enable accessibility of the latter to immune cells, rendering it a tumor‐associated antigen. Synthetic vaccines based on MUC1 tandem repeat motifs, comprising tumor‐associated 2,3‐sialyl‐T antigen, conjugated to the immunostimulating tetanus toxoid, are reported herein. Immunization with these vaccines in a simple water/oil emulsion produced a strong immune response in mice to which stimulation with complete Freund's adjuvant (CFA) was not superior. In both cases, high levels of IgG1 and IgG2a/b were induced in C57BL/6 mice. Additional glycosylation in the immunodominant PDTRP domain led to improved binding of the induced antisera to MCF‐7 breast tumor cells, compared with that of the monoglycosylated peptide vaccine. |
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Keywords: | antitumor agents cancer glycopeptides regioselective sialylation synthetic vaccines |
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