Open AccessA novel tumor‐associated antigen, cell division cycle 45‐like can induce cytotoxic T‐lymphocytes reactive to tumor cells
Author(s) -
Tomita Yusuke,
Imai Katsunori,
Senju Satoru,
Irie Atsushi,
Inoue Mitsuhiro,
Hayashida Yuki,
Shiraishi Kenji,
Mori Takeshi,
Daigo Yataro,
Tsunoda Takuya,
Ito Takaaki,
Nomori Hiroaki,
Nakamura Yusuke,
Kohrogi Hirotsugu,
Nishimura Yasuharu
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.01865.x
Subject(s) - ctl* , cytotoxic t cell , antigen , lung cancer , immunotherapy , adoptive cell transfer , epitope , cancer research , biology , immunology , cancer immunotherapy , cancer , cd8 , t cell , immune system , medicine , in vitro , pathology , biochemistry , genetics
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. ( Cancer Sci 2011; 102: 697–705)