Antibody Induction Directed against the Tumor‐Associated MUC4 Glycoprotein |
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Authors: | Dr Hui Cai Björn Palitzsch Dr Sebastian Hartmann Natascha Stergiou Prof Dr Horst Kunz Prof Dr Edgar Schmitt Dr Ulrika Westerlind |
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Affiliation: | 1. Gesellschaft zur F?rderung der Analytischen Wissenschaften e.V. ISAS–Leibniz Institute for Analytical Sciences, Otto‐Hahn‐Strasse 6b, 44227 Dortmund (Germany).;2. Institut für Organische Chemie, Johannes Gutenberg‐Universit?t Mainz, Duesbergweg 10–14, 55128 Mainz (Germany).;3. University Medical Center, Institute of Immunology, Johannes Gutenberg‐Universit?t Mainz, Langenbeckstrasse 1, Geb. 708, 55101 Mainz (Germany) |
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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. |
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Keywords: | antibodies cancer glycopeptides microarrays vaccines |
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