1. Aurora kinase A-specific T-cell receptor gene transfer redirects T lymphocytes to display effective antileukemia reactivity.
- Author
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Nagai, Kozo, Ochi, Toshiki, Fujiwara, Hiroshi, An, Jun, Shirakata, Toshiaki, Mineno, Junichi, Kuzushima, Kiyotaka, Shiku, Hiroshi, Melenhorst, J. Joseph, Gostick, Emma, Price, David A., Ishii, Eiichi, and Yasukawa, Masaki
- Subjects
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AURORA kinases , *LEUKEMIA treatment , *T cells , *GENETIC transformation , *IMMUNOTHERAPY , *XENOGRAFTS - Abstract
Aurora kinase A (AURKA) is overexpressed in leukemias. Previously, we demonstrated that AURKA-specific CD8+ T-cells specifically and selectively lysed leukemia cells, indicating that AURKA is an excellent target for immunotherapy. In this study, we examined the feasibility of adoptive therapy using redirected T-cells expressing an HLA-A*0201-restricted AURKA207-215-specific T-cell receptor (TCR). Retrovirally transduced T-cells recognized relevant peptide-pulsed but not control target cells. Furthermore, TCR-redirected CD8+ T-cells lysed AURKA-overexpressing human leukemic cells in an HLA-A*0201-restricted manner, but did not kill HLA-A*0201+ normal cells, including hematopoietic progenitors. In addition, AURKA207-215-specific TCR-transduced CD4+ T-cells displayed target-responsive Th1 cytokine production. Finally, AURKA207-215-specific TCR-transduced CD8+ T-cells displayed anti-leukemia efficacy in a xenograft mouse model. Collectively, these data demonstrate the feasibility of redirected T-cell-based AURKA-specific immunotherapy for the treatment of human leukemia. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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