Breast cancer is the second leading cause of cancer death in women after lung cancer. Despite progress in the treatment of this cancer, survival rates remain poor for patients with metastatic breast cancer. A more effective preventative therapy or treatment for breast cancer is needed. The success of this project will be the first step in our overall goal of developing a subunit vaccine that will enable control of breast cancer in humans. This research activity aims to determine the feasibility of a plant-derived, breast cancer vaccine by determining if tolerance to the tumor associated antigen, mucin-1 (MUC1) can be broken using an orally delivered, plant-derived vaccine. An epitope from MUC1 was chosen for this study since: it has significant correlation to tumor grade; the re-orientation of the MUC1 protein allows access of anti-MUC1 antibodies to tumor sites that are mostly excluded from normal epithelial tissues; it is highly antigenic and it is found in two common forms of breast cancer. An epitope of MUC1 was fused to the B subunit (LTB) of the heat-labile toxin of enterotoxigenic Escherichia coil to target the MUC1 epitope to the antigen presenting cells beneath the lining of mucosal surfaces. We have inserted this fusion protein into a plant expression cassette and transformed Nicotiana benthamiana and Lycopersicon esculentum (tomato) with the resulting construct. Transgenic plant lines were regenerated and their characterization is underway. Characterization of the transgenic plants will entail establishing whether the gene was inserted into the plant genome and establishing correct folding and concentration of the antigens LTB and MUC1 epitope in plant materials. Plant lines displaying high antigen expression, or elite plants, will be processed by freeze-drying, and transferred to the Mayo Clinic, Scottsdale for testing in a mice feed trial. We believe the novel delivery approach of this vaccine has potential to provide a broad immune response more capable of decreasing if not preventing tumor burden.
| Pinkhasov, Julia; Alvarez, M Lucrecia; Rigano, M Manuela et al. (2011) Recombinant plant-expressed tumour-associated MUC1 peptide is immunogenic and capable of breaking tolerance in MUC1.Tg mice. Plant Biotechnol J 9:991-1001 |
| Pinkhasov, Julia; Alvarez, M Lucrecia; Pathangey, Latha B et al. (2010) Analysis of a cholera toxin B subunit (CTB) and human mucin 1 (MUC1) conjugate protein in a MUC1-tolerant mouse model. Cancer Immunol Immunother 59:1801-11 |
