Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients Journal Article
| Authors: | Ohue, Y.; Eikawa, S.; Okazaki, N.; Mizote, Y.; Isobe, M.; Uenaka, A.; Fukuda, M.; Old, L. J.; Oka, M.; Nakayama, E. |
| Article 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. © 2011 UICC. |
| Keywords: | controlled study; unclassified drug; human cell; major clinical study; case-control studies; carcinoma, squamous cell; drug targeting; cancer staging; neoplasm staging; adenocarcinoma; antigen expression; cd8+ t lymphocyte; cell proliferation; cd8-positive t-lymphocytes; allele; apoptosis; dendritic cell; embryo; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; tumor cells, cultured; tumor antigen; blotting, western; dendritic cells; lung adenocarcinoma; cellular immunity; antigens, neoplasm; gamma interferon; cancer vaccine; messenger rna; reverse transcriptase polymerase chain reaction; rna, messenger; immunogenicity; antibody response; antigen recognition; cd4+ t lymphocyte; cd4-positive t-lymphocytes; peptide fragments; epitope; lung; interferon-gamma; cancer/testis antigen; enzyme-linked immunosorbent assay; cell clone; cell stimulation; epitopes, t-lymphocyte; non-small cell lung cancer; antibodies, neoplasm; peripheral blood mononuclear cell; carcinoma, large cell; interferon production; real-time polymerase chain reaction; immunocytotoxicity; antibody and t-cell responses; xage-1b (gaged2a); xage 1b antigen; hla drb1 antigen |
| Journal Title: | International Journal of Cancer |
| Volume: | 131 |
| Issue: | 5 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2012-09-01 |
| Start Page: | E649 |
| End Page: | E658 |
| Language: | English |
| DOI: | 10.1002/ijc.27359 |
| PROVIDER: | scopus |
| PUBMED: | 22109656 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2012" - "CODEN: IJCNA" - "Source: Scopus" |
