RRC ID 18593
Author Ohue Y, Eikawa S, Okazaki N, Mizote Y, Isobe M, Uenaka A, Fukuda M, Old LJ, Oka M, Nakayama E.
Title Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients.
Journal Int J Cancer
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.
Volume 131(5)
Pages E649-58
Published 2012-9-1
DOI 10.1002/ijc.27359
PMID 22109656
MeSH Adenocarcinoma / genetics Adenocarcinoma / immunology Adenocarcinoma / metabolism Antibodies, Neoplasm / blood* Antibodies, Neoplasm / immunology Antigens, Neoplasm / genetics Antigens, Neoplasm / immunology* Antigens, Neoplasm / metabolism Apoptosis Blotting, Western CD4-Positive T-Lymphocytes / immunology* CD4-Positive T-Lymphocytes / metabolism CD4-Positive T-Lymphocytes / pathology CD8-Positive T-Lymphocytes / immunology* CD8-Positive T-Lymphocytes / metabolism CD8-Positive T-Lymphocytes / pathology Carcinoma, Large Cell / genetics Carcinoma, Large Cell / immunology Carcinoma, Large Cell / metabolism Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Non-Small-Cell Lung / immunology* Carcinoma, Non-Small-Cell Lung / metabolism Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / immunology Carcinoma, Squamous Cell / metabolism Case-Control Studies Cell Proliferation Dendritic Cells / immunology Dendritic Cells / metabolism Dendritic Cells / pathology Enzyme-Linked Immunosorbent Assay Epitopes, T-Lymphocyte / immunology Epitopes, T-Lymphocyte / metabolism Humans Interferon-gamma / metabolism Lung / immunology Lung / metabolism Lung Neoplasms / genetics Lung Neoplasms / immunology* Lung Neoplasms / metabolism Neoplasm Staging Peptide Fragments / immunology Prognosis RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured
IF 5.145
Times Cited 25
Human and Animal Cells 293T(RCB2202) RERF-LC-AI(RCB0444)