Abstract |
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.
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Authors | Yusuke Tomita, Katsunori Imai, Satoru Senju, Atsushi Irie, Mitsuhiro Inoue, Yuki Hayashida, Kenji Shiraishi, Takeshi Mori, Yataro Daigo, Takuya Tsunoda, Takaaki Ito, Hiroaki Nomori, Yusuke Nakamura, Hirotsugu Kohrogi, Yasuharu Nishimura |
Journal | Cancer science
(Cancer Sci)
Vol. 102
Issue 4
Pg. 697-705
(Apr 2011)
ISSN: 1349-7006 [Electronic] England |
PMID | 21231984
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2011 Japanese Cancer Association. |
Chemical References |
- Biomarkers, Tumor
- CDC45 protein, human
- Cell Cycle Proteins
- Epitopes
- HLA-A Antigens
- HLA-A24 Antigen
- Peptide Fragments
- RNA, Messenger
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Topics |
- Animals
- Biomarkers, Tumor
(genetics, metabolism)
- Blotting, Northern
- Blotting, Western
- Cell Cycle Proteins
(genetics, immunology, metabolism)
- Epitopes
(immunology)
- Gene Expression Profiling
- HLA-A Antigens
(immunology, metabolism)
- HLA-A24 Antigen
- Humans
- Immunoenzyme Techniques
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Neoplasms
(immunology, metabolism, therapy)
- Oligonucleotide Array Sequence Analysis
- Peptide Fragments
(immunology, metabolism)
- RNA, Messenger
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
- T-Lymphocytes, Cytotoxic
(immunology)
- Tumor Cells, Cultured
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