title: Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients.
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.
authors: Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Japan.
authors: Yoshihiro
authors: Y
authors: Ohue
authors: Shingo
authors: S
authors: Eikawa
authors: Nami
authors: N
authors: Okazaki
authors: Yu
authors: Y
authors: Mizote
authors: Midori
authors: M
authors: Isobe
authors: Akiko
authors: A
authors: Uenaka
authors: Minoru
authors: M
authors: Fukuda
authors: Lloyd J
authors: LJ
authors: Old
authors: Mikio
authors: M
authors: Oka
authors: Eiichi
authors: E
authors: Nakayama
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000097:blood* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000276:immunology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D012333:RNA, Messenger; C413656:XAGE1A protein, human; D007371:Interferon-gamma