Identification of MAGE-C1 (CT-7) epitopes for T-cell therapy of multiple myeloma.

Publication Type:

Journal Article

Source:

Cancer immunology, immunotherapy : CII, Volume 60, Issue 7, p.985-97 (2011)

Keywords:

2011, Animals, Antigen Presentation, Antigens, Neoplasm, Center-Authored Paper, Clinical Research Division, DENDRITIC CELLS, Epitopes, T-Lymphocyte, Flow Cytometry Core Facility, HLA-A2 Antigen, Humans, IMMUNOTHERAPY, interferon-gamma, MICE, Mice, Transgenic, Multiple Myeloma, Neoplasm Proteins, Peptide Fragments, Scientific Imaging Core Facility, September 2011, Shared Resources, T-Lymphocytes, Cytotoxic, Tumor Cells, Cultured, Vaccination

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.