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Synthetic MUC1 Antitumor Vaccine with Incorporated 2,3‐Sialyl‐T Carbohydrate Antigen Inducing Strong Immune Responses with Isotype Specificity
Author(s) -
Straßburger David,
Glaffig Markus,
Stergiou Natascha,
Bialas Sabrina,
Besenius Pol,
Schmitt Edgar,
Kunz Horst
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800148
Subject(s) - immune system , antigen , muc1 , adjuvant , glycan , glycosylation , immunology , biology , chemistry , glycoprotein , microbiology and biotechnology , biochemistry
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.