title: 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: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Larry.Anderson@UTSouthwestern.edu
authors: Larry D
authors: LD
authors: Anderson
authors: Danielle R
authors: DR
authors: Cook
authors: Tori N
authors: TN
authors: Yamamoto
authors: Carolina
authors: C
authors: Berger
authors: David G
authors: DG
authors: Maloney
authors: Stanley R
authors: SR
authors: Riddell
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000502:physiology; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; C110905:MAGEC1 protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D007371:Interferon-gamma