Aurora-A kinase: a novel target of cellular immunotherapy for leukemia
Aurora-A kinase: a novel target of cellular immunotherapy for leukemia
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DOI：
10.1182/blood-2008-06-164889
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发表时间：
2009-01-01
期刊：
影响因子：
20.3
通讯作者：
Yasukawa, Masaki
中科院分区：
文献类型：
--
作者：
Ochi, Toshiki;Fujiwara, Hiroshi;Yasukawa, Masaki
Aurora-A激酶（Aur-A）是调节细胞分裂过程的丝氨酸/苏氨酸激酶家族的成员，并且最近与肿瘤发生有关。在这项研究中，我们确定了一个抗原性的9个氨基酸的表位（Aur-A（207-215）：YLILEYAPL），来自Aur-A能够产生白血病反应性细胞毒性T淋巴细胞（CTL）在HLA-A*0201的背景下。该表位的合成肽似乎能够结合HLA-A*2402以及HLA-A*0201分子。白血病细胞系和新鲜分离的白血病细胞，特别是慢性髓性白血病（CML）细胞，似乎大量表达Aur-A。Aur-A特异性CTL能够以HLA-A*0201限制性方式裂解人白血病细胞系和新鲜分离的白血病细胞，但不能裂解正常细胞。重要的是，Aur-A特异性CTL能够裂解CD 34（+）CML祖细胞，但对正常CD 34（+）造血干细胞没有任何细胞毒性。四聚体检测结果显示，HLA-A*0201阳性和HLA-A*2402阳性的白血病患者外周血中存在Aur-A（207-215）表位特异性CTL前体，而健康人外周血中不存在。我们的研究结果表明，靶向Aur-A的细胞免疫治疗是一种很有前途的治疗白血病的策略。（血。2009; 113：66-74）
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-A(207-215): 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-A(207-215) 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. (Blood. 2009; 113: 66-74)