title: Antibody induction directed against the tumor-associated MUC4 glycoprotein.
abstract: 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.
authors.affiliation: Gesellschaft zur Förderung der Analytischen Wissenschaften e.V. ISAS-Leibniz Institute for Analytical Sciences, Otto-Hahn-Strasse 6b, 44227 Dortmund (Germany).
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Björn
authors.initials: B
authors.lastname: Palitzsch
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hartmann
authors.forename: Natascha
authors.initials: N
authors.lastname: Stergiou
authors.forename: Horst
authors.initials: H
authors.lastname: Kunz
authors.forename: Edgar
authors.initials: E
authors.lastname: Schmitt
authors.forename: Ulrika
authors.initials: U
authors.lastname: Westerlind
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000918:Antibody Specificity; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D055264:Mucin-4 / Q000737:chemistry / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology; D020080:Tandem Repeat Sequences; D013745:Tetanus Toxoid / Q000737:chemistry; D014611:Vaccination
chemical_list: D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D007106:Immune Sera; D055264:Mucin-4; D013745:Tetanus Toxoid
keywords: antibodies; cancer; glycopeptides; microarrays; vaccines