Identification of human leukocyte antigen-A24-restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy

Cancer Sci. 2007 Nov;98(11):1803-8. doi: 10.1111/j.1349-7006.2007.00603.x.

Abstract

For the development of cancer vaccine therapies, we have searched for possible epitope peptides that can elicit cytotoxic T lymphocytes (CTL) to the TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K) and insulin-like growth factor (IGF)-II mRNA binding protein 3 (IMP-3), which were previously identified to be transactivated in the majority of lung and esophageal cancers. We screened 31, 17 and 17 candidate human leukocyte antigen (HLA)-A*2402-binding peptides to parts of TTK, LY6K and IMP-3, respectively. As a result, we successfully established strong CTL clones stimulated by TTK-567 (SYRNEIAYL), LY6K-177 (RYCNLEGPPI) and IMP-3-508 (KTVNELQNL) that have specific cytotoxic activities against the HLA-A24-positive target cells pulsed with the candidate peptides. Subsequent analysis of the CTL clones also revealed their cytotoxic activities against lung and esophageal tumor cells that endogenously express TTK, LY6K or IMP-3. A cold target inhibition assay further confirmed that the CTL cell clones specifically recognized the MHC class I–peptide complex. Our results strongly imply that TTK, LY6K and IMP-3 are novel tumor-associated antigens recognized by CTL, and TTK-567 (SYRNEIAYL), LY6K-177 (RYCNLEGPPI) and IMP-3-508 (KTVNELQNL) are HLA-A24-restricted epitope peptides that can induce potent and specific immune responses against lung and esophageal cancer cells expressing TTK, LY6K and IMP-3.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Ly / genetics
  • Antigens, Ly / immunology
  • Antigens, Ly / metabolism
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology*
  • Biomarkers, Tumor / metabolism
  • Cancer Vaccines / immunology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / immunology
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytotoxicity Tests, Immunologic / methods
  • Cytotoxicity, Immunologic / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Epitopes, T-Lymphocyte / metabolism
  • Esophageal Neoplasms / immunology
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology
  • GPI-Linked Proteins / metabolism
  • HLA-A24 Antigen / immunology*
  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Peptides / genetics
  • Peptides / immunology*
  • Peptides / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / immunology
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / immunology
  • RNA-Binding Proteins / metabolism
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Antigens, Ly
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cancer Vaccines
  • Cell Cycle Proteins
  • Epitopes, T-Lymphocyte
  • GPI-Linked Proteins
  • HLA-A*24:02 antigen
  • HLA-A24 Antigen
  • IGF2BP3 protein, human
  • LY6K protein, human
  • Peptides
  • RNA-Binding Proteins
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • TTK protein, human