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Antibody Induction Directed against the Tumor‐Associated MUC4 Glycoprotein
Author(s) -
Cai Hui,
Palitzsch Björn,
Hartmann Sebastian,
Stergiou Natascha,
Kunz Horst,
Schmitt Edgar,
Westerlind Ulrika
Publication year - 2015
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.201402689
Subject(s) - glycopeptide , immunogenicity , muc1 , epitope , glycoprotein , antigen , antibody , immune system , glycosylation , cancer vaccine , biology , microbiology and biotechnology , immunology , immunotherapy , biochemistry , antibiotics
Mucin glycoproteins are important diagnostic and therapeutic targets for cancer treatment. Although several strategies have been developed to explore anti‐tumor vaccines based on MUC1 glycopeptides, only few studies have focused on vaccines directed against the tumor‐associated MUC4 glycoprotein. MUC4 is an important tumor marker overexpressed in lung cancer and uniquely expressed in pancreatic ductual adenocarcinoma. The aberrant glycosylation of MUC4 in tumor cells results in an exposure of its peptide backbone and the formation of tumor‐associated glycopeptide antigens. Due to the low immunogenicity of these endogenous structures, their conjugation with immune stimulating peptide or protein carriers are required. In this study, MUC4 tandem‐repeat glycopeptides were conjugated to the tetanus toxoid and used for vaccination of mice. Immunological evaluations showed that our MUC4‐based vaccines induced very strong antigen‐specific immune responses. In addition, antibody binding epitope analysis on glycopeptide microarrays, were demonstrating a clear glycosylation site dependence of the induced antibodies.

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