| Autor: |
Soysal, S., Muenst, S., Kan-Mitchell, J., Huarte, E., Zhang, X., Wilkinson-Ryan, I., Fleming, T., Tiriveedhi, V., Mohanakumar, T., Li, L., Herndon, J., Oertli, D., Goedegebuure, S., Gillanders, W. |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Popis: |
Mammaglobin-A (MAM-A) is a secretory protein that is overexpressed in 80% of human breast cancers. Its near-universal expression in breast cancer as well as its exquisite tissue specificity makes it an attractive target for a breast cancer prevention vaccine, and we recently initiated a phase 1 clinical trial of a MAM-A DNA vaccine. Previously, we have identified multiple MAM-A CD8 T cell epitopes using a reverse immunology candidate epitope approach based on predicted binding, but to date no attempt has been made to identify epitopes using an unbiased approach. In this study, we used human T cells primed in vitro with autologous dendritic cells expressing MAM-A to systematically identify MAM-A CD8 T cell epitopes. Using this unbiased approach, we identified three novel HLA-A2-restricted MAM-A epitopes. CD8 T cells specific for these epitopes are able to recognize and lyse human breast cancer cells in a MAM-A-specific, HLA-A2-dependent fashion. HLA-A2+/MAM-A+ breast cancer patients have an increased prevalence of CD8 T cells specific for these novel MAM-A epitopes, and vaccination with a MAM-A DNA vaccine significantly increases the number of these CD8 T cells. The identification and translational validation of novel MAM-A epitopes has important implications for the ongoing clinical development of vaccine strategies targeting MAM-A. The novel MAM-A epitopes represent attractive targets for epitope-based vaccination strategies, and can also be used to monitor immune responses. Taken together these studies provide additional support for MAM-A as an important therapeutic target for the prevention and treatment of breast cancer. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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