| RRC ID |
17618
|
| 著者 |
Tomita Y, Imai K, Senju S, Irie A, Inoue M, Hayashida Y, Shiraishi K, Mori T, Daigo Y, Tsunoda T, Ito T, Nomori H, Nakamura Y, Kohrogi H, Nishimura Y.
|
| タイトル |
A novel tumor-associated antigen, cell division cycle 45-like can induce cytotoxic T-lymphocytes reactive to tumor cells.
|
| ジャーナル |
Cancer Sci
|
| 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.
|
| 巻・号 |
102(4)
|
| ページ |
697-705
|
| 公開日 |
2011-4-1
|
| DOI |
10.1111/j.1349-7006.2011.01865.x
|
| PMID |
21231984
|
| MeSH |
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
|
| IF |
4.966
|
| 引用数 |
25
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
PANC-1(RCB2095)
T2(RCB1932) |
