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

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.

• Authors: Larry D Anderson Jr, Danielle R Cook, Tori N Yamamoto, Carolina Berger, David G Maloney, Stanley R Riddell
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 60 Issue 7 Pg. 985-97 (Jul 2011) ISSN: 1432-0851 [Electronic] Germany
• PMID: 21461886 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Epitopes, T-Lymphocyte
• HLA-A2 Antigen
• MAGEC1 protein, human
• Neoplasm Proteins
• Peptide Fragments
• Interferon-gamma

Topics

• Animals
• Antigen Presentation
• Antigens, Neoplasm (genetics, immunology)
• Dendritic Cells (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Flow Cytometry
• HLA-A2 Antigen (physiology)
• Humans
• Immunotherapy
• Interferon-gamma (metabolism)
• Mice
• Mice, Transgenic
• Multiple Myeloma (genetics, immunology, therapy)
• Neoplasm Proteins (genetics, immunology)
• Peptide Fragments (administration & dosage, immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Cells, Cultured
• Vaccination