Aurora-A kinase: a novel target of cellular immunotherapy for leukemia.
Blood
; 113(1): 66-74, 2009 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-18820130
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T Citotóxicos
/
Leucemia Mielógena Crónica BCR-ABL Positiva
/
Inmunoterapia Adoptiva
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Proteínas Serina-Treonina Quinasas
Límite:
Humans
Idioma:
En
Revista:
Blood
Año:
2009
Tipo del documento:
Article
País de afiliación:
Japón