Antibody Induction Directed against the Tumor‐Associated MUC4 Glycoprotein

ChemBioChem - Tập 16 Số 6 - Trang 959-967 - 2015
Hui Cai1, Björn Palitzsch2, Sebastian Hartmann2, Natascha Stergiou3, Horst Kunz2, Edgar Schmitt4,5,3, Ulrika Westerlind4,1,5
1Gesellschaft zur Förderung der Analytischen Wissenschaften e.V. ISAS–Leibniz Institute for Analytical Sciences, Otto-Hahn-Strasse 6b, 44227 Dortmund (Germany).
2Institut für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10–14, 55128 Mainz (Germany).
3University Medical Center, Institute of Immunology, Johannes Gutenberg-Universität Mainz, Langenbeckstrasse 1, Geb. 708, 55101 Mainz (Germany)
4Edgar Schmitt, University Medical Center, Institute of Immunology, Johannes Gutenberg-Universität Mainz, Langenbeckstrasse 1, Geb. 708, 55101 Mainz (Germany)
5Ulrika Westerlind, Gesellschaft zur Förderung der Analytischen Wissenschaften e.V. ISAS–Leibniz Institute for Analytical Sciences, Otto-Hahn-Strasse 6b, 44227 Dortmund (Germany).

Tóm tắt

AbstractMucin 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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Tài liệu tham khảo

 

10.3109/10409239209082559

10.1042/bst0230795

10.1042/bst0250214

 

10.1126/science.6729450

10.1111/j.1432-1033.1995.607_2.x

10.1016/S0304-4165(99)00170-1

10.1074/jbc.271.52.33325

 

10.1126/science.291.5512.2370

10.1038/nrc2761

10.1016/S0925-4439(99)00055-1

 

10.1002/anie.199508031

10.1002/ange.19951070726

10.1002/anie.200902564

10.1002/ange.200902564

10.1002/anie.201308875

10.1002/ange.201308875

10.1002/chem.201203709

10.1073/pnas.1115166109

10.1002/anie.201006115

10.1002/ange.201006115

10.1021/ja4046857

10.1039/c3cs35470a

10.1002/anie.201104529

10.1002/ange.201104529

10.1002/anie.201003810

10.1002/ange.201003810

 

10.1096/fj.07-9673rev

10.1038/modpathol.3800027

 

10.1002/dc.20771

Kwon K. Y., 2007, Arch. Pathol. Lab. Med., 131, 593, 10.5858/2007-131-593-MEINCL

10.1136/jcp.2004.023572

10.1038/modpathol.3800445

 

10.3390/cancers2041794

10.1371/journal.pone.0032232

Andrianifahanana M., 2001, Clin. Cancer Res., 7, 4033

10.1309/7Y7N-M1WM-R0YK-M2VA

 

10.1021/bc200606s

Brocke C., 2004, Synthesis, 525

Brocke C., 2003, Synlett, 2052

10.1002/chem.200400228

10.1002/anie.200700964

10.1002/ange.200700964

10.1016/j.carres.2008.05.003

 

10.1002/anie.200902963

10.1002/ange.200902963

10.1158/0008-5472.CAN-09-2893

10.1002/ijc.25778

10.1186/bcr2841

10.1016/j.cbpa.2014.01.002

10.1021/bc00009a003

 

10.1002/1521-3773(20010119)40:2<366::AID-ANIE366>3.0.CO;2-J

10.1002/1521-3757(20010119)113:2<379::AID-ANGE379>3.0.CO;2-S

Brocke C., 2003, Synlett, 2052

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ChemBioChem

Tập 16 Số 6

959-967

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