Aurora-A kinase: a novel target of cellular immunotherapy for leukemia

• Published in: Blood Vol. 113; no. 1; pp. 66 - 74
• Main Authors: Ochi, Toshiki, Fujiwara, Hiroshi, Suemori, Koichiro, Azuma, Taichi, Yakushijin, Yoshihiro, Hato, Takaaki, Kuzushima, Kiyotaka, Yasukawa, Masaki
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.01.2009; Americain Society of Hematology
• Subjects: Antigens, CD34 - metabolism; Aurora Kinases; Biological and medical sciences; Cell Line, Tumor; Epitopes - immunology; Hematologic and hematopoietic diseases; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; HLA-A Antigens - metabolism; HLA-A2 Antigen; HLA-A24 Antigen; Humans; Immunotherapy, Adoptive - methods; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes, Mononuclear - cytology; Medical sciences; Mitosis; Peptide Fragments - genetics; Peptide Fragments - immunology; Peptide Fragments - metabolism; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - immunology; Protein-Serine-Threonine Kinases - metabolism; RNA, Messenger - metabolism; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Human; Antigenic determinant; Acquired immunity; Enzyme; Targeted therapy; Leukemia; Malignant hemopathy; Cellular immunity; Aurora kinase; Serine/threonine-protein kinase 6; Treatment; Immunotherapy; Cytotoxic T lymphocyte; Cancer
• DOI: 10.1182/blood-2008-06-164889
• ISSN: 0006-4971; 1528-0020

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.