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

TY - JOUR

T1 - Identification of MAGE-C1 (CT-7) epitopes for T-cell therapy of multiple myeloma

AU - Anderson, Larry D

AU - Cook, Danielle R

AU - Yamamoto, Tori N

AU - Berger, Carolina

AU - Maloney, David G

AU - Riddell, Stanley R

PY - 2011/7

Y1 - 2011/7

N2 - 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.

AB - 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.

KW - Animals

KW - Antigen Presentation

KW - Antigens, Neoplasm/genetics

KW - Dendritic Cells/immunology

KW - Epitopes, T-Lymphocyte/immunology

KW - Flow Cytometry

KW - HLA-A2 Antigen/physiology

KW - Humans

KW - Immunotherapy

KW - Interferon-gamma/metabolism

KW - Mice

KW - Mice, Transgenic

KW - Multiple Myeloma/genetics

KW - Neoplasm Proteins/genetics

KW - Peptide Fragments/administration & dosage

KW - T-Lymphocytes, Cytotoxic/immunology

KW - Tumor Cells, Cultured

KW - Vaccination

U2 - 10.1007/s00262-011-1009-3

DO - 10.1007/s00262-011-1009-3

M3 - SCORING: Journal article

C2 - 21461886

VL - 60

SP - 985

EP - 997

JO - CANCER IMMUNOL IMMUN

JF - CANCER IMMUNOL IMMUN

SN - 0340-7004

IS - 7

ER -