A novel tumor-associated antigen, cell division cycle 45-like can induce cytotoxic T-lymphocytes reactive to tumor cells

Cancer Sci. 2011 Apr;102(4):697-705. doi: 10.1111/j.1349-7006.2011.01865.x. Epub 2011 Feb 10.


The present study attempted to identify a useful tumor-associated antigen (TAA) for lung cancer immunotherapy and potential immunogenic peptides derived from the TAA. We focused on cell division cycle 45-like (CDC45L), which has a critical role in the initiation and elongation steps of DNA replication, as a novel candidate TAA for immunotherapy based on a genome-wide cDNA microarray analysis of lung cancer. The CDC45L was overexpressed in the majority of lung cancer tissues, but not in the adjacent non-cancerous tissues or in many normal adult tissues. We examined the in vitro and in vivo anti-tumor effects of cytotoxic T-lymphocytes (CTL) specific to CDC45L-derived peptides induced from HLA-A24 (A*24:02)-positive donors. We identified three CDC45L-derived peptides that could reproducibly induce CDC45L-specific and HLA-A24-restricted CTL from both healthy donors and lung cancer patients. The CTL could effectively lyse lung cancer cells that endogenously expressed both CDC45L and HLA-A24. In addition, we found that CDC45L (556) KFLDALISL(564) was eminent in that it induced not only HLA-A24 but also HLA-A2 (A*02:01)-restricted antigen specific CTL. Furthermore, the adoptive transfer of the CDC45L-specific CTL inhibited the growth of human cancer cells engrafted into immunocompromised mice. These results suggest that these three CDC45L-derived peptides are highly immunogenic epitopes and CDC45L is a novel TAA that might be a useful target for lung cancer immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blotting, Northern
  • Blotting, Western
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / immunology
  • Cell Cycle Proteins / metabolism*
  • Epitopes / immunology*
  • Gene Expression Profiling
  • HLA-A Antigens / immunology*
  • HLA-A Antigens / metabolism
  • HLA-A24 Antigen
  • Humans
  • Immunoenzyme Techniques
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Oligonucleotide Array Sequence Analysis
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured


  • Biomarkers, Tumor
  • CDC45 protein, human
  • Cell Cycle Proteins
  • Epitopes
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Peptide Fragments
  • RNA, Messenger