Abstract
Multiple myeloma is incurable with standard therapies but is susceptible to a T-cell-mediated graft versus myeloma effect after allogeneic stem cell transplantation. We sought to identify myeloma-specific antigens that might be used for T-cell immunotherapy of myeloma. MAGE-C1 (CT-7) is a cancer-testis antigen that is expressed by tumor cells in >70% of myeloma patients and elicits a humoral response in up to 93% of patients with CT-7+ myeloma. No CD8+ T-cell epitopes have been described for CT-7, so we used a combination of reverse immunology and immunization of HLA-A2 transgenic mice with a novel cell-based vaccine to identify three immunogenic epitopes of CT-7 that are recognized by human CD8+ T-cells. CT-7-specific T-cells recognizing two of these peptides are able to recognize myeloma cells as well as CT-7 gene-transduced tumor cells, demonstrating that these epitopes are naturally processed and presented by tumor cells. This is the first report of the identification of immunogenic CD8+ T-cell epitopes of MAGE-C1 (CT-7), which is the most commonly expressed cancer-testis antigen found in myeloma, and these epitopes may be promising candidate targets for vaccination or T-cell therapy of myeloma or other CT-7+ malignancies.
Original language | English (US) |
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Pages (from-to) | 985-997 |
Number of pages | 13 |
Journal | Cancer Immunology, Immunotherapy |
Volume | 60 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2011 |
Keywords
- CT-7
- Cancer immunology
- Immunotherapy
- MAGE-C1
- Multiple myeloma
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Oncology
- Cancer Research