Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients

Yoshihiro Ohue, Shingo Eikawa, Nami Okazaki, Yu Mizote, Midori Isobe, Akiko Uenaka, Minoru Fukuda, Lloyd J. Old, Mikio Oka, Eiichi Nakayama

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27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)E649-E658
JournalInternational Journal of Cancer
Volume131
Issue number5
DOIs
Publication statusPublished - Sep 1 2012

Keywords

  • Antibody and T-cell responses
  • Cancer vaccine
  • Cancer/testis antigen
  • Non-small cell lung cancer
  • XAGE-1b (GAGED2a)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ohue, Y., Eikawa, S., Okazaki, N., Mizote, Y., Isobe, M., Uenaka, A., Fukuda, M., Old, L. J., Oka, M., & Nakayama, E. (2012). Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients. International Journal of Cancer, 131(5), E649-E658. https://doi.org/10.1002/ijc.27359