Abstract
The spontaneous immune responses against XAGE-1b (GAGED2a) were analyzed in non-small cell lung cancer (NSCLC) patients. An antibody response against XAGE-1b (GAGED2a) was observed in 10% (20/200) of NSCLC patients and in 19% (13/69) of stage IIIB/IV lung adenocarcinoma patients. A CD4 T-cell response was detected in 88% (14/16) and a CD8 T-cell response in 67% (6/9) in the XAGE-1b (GAGED2a) antibody-positive patients examined. Frequent antibody responses and CD4 and CD8 T-cell responses in XAGE-1b (GAGED2a) antibody-positive patients indicate the strong immunogenicity of the XAGE-1b (GAGED2a) antigen in NSCLC patients. We established T-cell clones from PBMCs of antibody-positive patients and determined the DRB1*04:05-restricted XAGE-1b (GAGED2a) 18-31 peptide (14-mer) as a CD4 T cell epitope and the A*02:06-restricted XAGE-1b (GAGED2a) 21-29 peptide (9-mer) as a CD8 T cell epitope. As for peptide recognition, CD4 and CD8 T-cell clones responded to naturally processed antigen. The CD4 T-cell clone recognized DCs pulsed with the synthetic protein or a lysate from XAGE-1b-transfected 293T cells. The CD8 T-cell clone showed cytotoxicity against a tumor expressing XAGE-1b (GAGED2a) and the appropriate HLA class I allele. These findings establish XAGE-1b (GAGED2a) as a promising target for a lung cancer vaccine.
Copyright © 2011 UICC.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / immunology
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Adenocarcinoma / metabolism
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Antibodies, Neoplasm / blood*
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Antibodies, Neoplasm / immunology
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology*
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Antigens, Neoplasm / metabolism
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Apoptosis
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Blotting, Western
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / pathology
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Carcinoma, Large Cell / genetics
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Carcinoma, Large Cell / immunology
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Carcinoma, Large Cell / metabolism
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / immunology*
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / immunology
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Carcinoma, Squamous Cell / metabolism
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Case-Control Studies
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Cell Proliferation
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dendritic Cells / pathology
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Enzyme-Linked Immunosorbent Assay
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism
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Humans
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Interferon-gamma / metabolism
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Lung / immunology
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Lung / metabolism
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Lung Neoplasms / genetics
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Lung Neoplasms / immunology*
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Lung Neoplasms / metabolism
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Neoplasm Staging
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Peptide Fragments / immunology
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Prognosis
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
Substances
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Antibodies, Neoplasm
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Antigens, Neoplasm
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Epitopes, T-Lymphocyte
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Peptide Fragments
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RNA, Messenger
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XAGE1A protein, human
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Interferon-gamma