Identification of MAGE-C1 (CT-7) epitopes for T-cell therapy of multiple myeloma
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Identification of MAGE-C1 (CT-7) epitopes for T-cell therapy of multiple myeloma. / Anderson, Larry D; Cook, Danielle R; Yamamoto, Tori N; Berger, Carolina; Maloney, David G; Riddell, Stanley R.
in: CANCER IMMUNOL IMMUN, Jahrgang 60, Nr. 7, 07.2011, S. 985-97.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -