Recombinant plant-expressed tumour-associated MUC1 peptide is immunogenic and capable of breaking tolerance in MUC1.Tg mice
| Autor: | Amanda Maree Walmsley, Sandra J. Gendler, Hugh S. Mason, M. Lucrecia Alvarez, Josephine Grass, Pinku Mukherjee, Maria Manuela Rigano, Julia Pinkhasov, Khanrat Piensook, Dalia Larios, Martin Pabst |
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| Rok vydání: | 2011 |
| Předmět: |
Antigenicity
Glycosylation biology medicine.drug_class Mucin Plant Science Monoclonal antibody digestive system Fusion protein Molecular biology biological factors digestive system diseases chemistry.chemical_compound chemistry Antigen biology.protein medicine Antibody skin and connective tissue diseases neoplasms Agronomy and Crop Science MUC1 Biotechnology |
| Zdroj: | Plant Biotechnology Journal. 9:991-1001 |
| ISSN: | 1467-7644 |
| DOI: | 10.1111/j.1467-7652.2011.00614.x |
| Popis: | Summary The human epithelial mucin MUC1 is a heavily glycosylated transmembrane protein that is overexpressed and aberrantly glycosylated on over 90% of human breast cancers. The altered glycosylation of MUC1 reveals an immunodominant peptide along its tandem repeat (TR) that has been used as a target for tumour immunotherapy. In this study, we used the MUC1 TR peptide as a test antigen to determine whether a plant-expressed human tumour-associated antigen can be successfully expressed in a plant system and whether it will be able to break self-antigen tolerance in a MUC1-tolerant mouse model. We report the expression of MUC1 TR peptide fused to the mucosal-targeting Escherichia coli enterotoxin B subunit (LTB-MUC1) in a plant host. Utilizing a rapid viral replicon transient expression system, we obtained high yields of LTB-MUC1. Importantly, the LTB-MUC1 fusion protein displayed post-translational modifications that affected its antigenicity. Glycan analysis revealed that LTB-MUC1 was glycosylated and a MUC1-specific monoclonal antibody detected only the glycosylated forms. A thorough saccharide analysis revealed that the glycans are tri-arabinans linked to hydroxyprolines within the MUC1 tandem repeat sequence. We immunized MUC1-tolerant mice (MUC1.Tg) with transiently expressed LTB-MUC1, and observed production of anti-MUC1 serum antibodies, indicating breach of tolerance. The results indicate that a plant-derived human tumour-associated antigen is equivalent to the human antigen in the context of immune recognition. |
| Databáze: | OpenAIRE |
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