Submitted June 25, 2008
Accepted September 6, 2008
Aurora-A kinase: A novel target of cellular immunotherapy for leukemia
Toshiki Ochi, Hiroshi Fujiwara, Koichiro Suemori, Taichi Azuma, Yoshihiro Yakushijin, Takaaki Hato, Kiyotaka Kuzushima, and Masaki Yasukawa*
Department of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
Cancer Center, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
Division of Blood Transfusion and Cell Therapy, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
Division of Immunology, Aichi Cancer Center, Nagoya, Aichi, Japan
Center for Regenerative Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
* Corresponding author; email: yasukawa{at}m.ehime-u.ac.jp.
Aurora-A kinase (Aur-A) is a member of the serine/threonine kinase family that regulates the cell division process, and has recently been implicated in tumorigenesis. In this study, we identified an antigenic 9-amino-acid epitope (Aur-A207-215: YLILEYAPL) derived from Aur-A capable of generating leukemia-reactive cytotoxic T lymphocytes (CTLs) in the context of HLA-A*0201. The synthetic peptide of this epitope appeared to be capable of binding to HLA-A*2402 as well as HLA-A*0201 molecules. Leukemia cell lines and freshly isolated leukemia cells, particularly chronic myelogenous leukemia (CML) cells, appeared to express Aur-A abundantly. Aur-A-specific CTLs were able to lyse human leukemia cell lines and freshly isolated leukemia cells, but not normal cells, in an HLA-A*0201-restricted manner. Importantly, Aur-A-specific CTLs were able to lyse CD34+ CML progenitor cells but did not show any cytotoxicity against normal CD34+ hematopoietic stem cells. The tetramer assay revealed that the Aur-A207-215 epitope-specific CTL precursors are present in peripheral blood of HLA-A*0201-positive and HLA-A*2402-positive patients with leukemia, but not in healthy individuals. Our results indicate that cellular immunotherapy targeting Aur-A is a promising strategy for treatment of leukemia.
