Next Article in Journal
Enhanced Antioxidant Activity of Bioactives in Colored Grains by Nano-Carriers in Human Lens Epithelial Cells
Next Article in Special Issue
Role of O-Acetylation in the Immunogenicity of Bacterial Polysaccharide Vaccines
Previous Article in Journal
Development and Validation of a HPLC-MS/MS Method for Simultaneous Determination of Twelve Bioactive Compounds in Epimedium: Application to a Pharmacokinetic Study in Rats
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessReview
Molecules 2018, 23(6), 1326; https://doi.org/10.3390/molecules23061326

Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy

1
Shanghai Pulmonary Hospital Affiliated with Tongji University School of Medicine, Shanghai 200092, China
2
Laboratory of Antibody Structure, Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201203, China
3
CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences and iHuman Institute, ShanghaiTech University, Shanghai 201203, China
4
Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, D-01307 Dresden, Germany
5
Medical Faculty, Carl Gustav Carus Technical University Dresden, D-01307 Dresden, Germany
*
Authors to whom correspondence should be addressed.
Academic Editors: Paul Kovac, Peng Xu and Helene Pfister
Received: 1 May 2018 / Revised: 20 May 2018 / Accepted: 22 May 2018 / Published: 31 May 2018
(This article belongs to the Special Issue Conjugate Vaccines from Carbohydrate Antigens)
Full-Text   |   PDF [4257 KB, uploaded 31 May 2018]   |  

Abstract

Abnormally O-glycosylated MUC1 tandem repeat glycopeptide epitopes expressed by multiple types of cancer have long been attractive targets for therapy in the race against genetic mutations of tumor cells. Glycopeptide signature-guided therapy might be a more promising avenue than mutation signature-guided therapy. Three O-glycosylated peptide motifs, PDTR, GSTA, and GVTS, exist in a tandem repeat HGVTSAPDTRPAPGSTAPPA, containing five O-glycosylation sites. The exact peptide and sugar residues involved in antibody binding are poorly defined. Co-crystal structures of glycopeptides and respective monoclonal antibodies are very few. Here we review 3 groups of monoclonal antibodies: antibodies which only bind to peptide portion, antibodies which only bind to sugar portion, and antibodies which bind to both peptide and sugar portions. The antigenicity of peptide and sugar portions of glyco-MUC1 tandem repeat were analyzed according to available biochemical and structural data, especially the GSTA and GVTS motifs independent from the most studied PDTR. Tn is focused as a peptide-modifying residue in vaccine design, to induce glycopeptide-binding antibodies with cross reactivity to Tn-related tumor glycans, but not glycans of healthy cells. The unique requirement for the designs of antibody in antibody-drug conjugate, bi-specific antibodies, and chimeric antigen receptors are also discussed. View Full-Text
Keywords: MUC1; tandem repeat; antibodies; glycopeptide; co-crystal MUC1; tandem repeat; antibodies; glycopeptide; co-crystal
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Zhou, D.; Xu, L.; Huang, W.; Tonn, T. Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy. Molecules 2018, 23, 1326.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top