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Aurora kinase A-specific T-cell receptor gene transfer redirects T lymphocytes to display effective antileukemia reactivity

Nagai, Kozo, Ochi, Toshiki, Fujiwara, Hiroshi, An, Jun, Shirakata, Toshiaki, Mineno, Junichi, Kuzushima, Kiyotaka, Shiku, Hiroshi, Melenhorst, J. Joseph, Gostick, Emma, Price, David, Ishii, Eiichi and Yasukawa, Masaki 2011. Aurora kinase A-specific T-cell receptor gene transfer redirects T lymphocytes to display effective antileukemia reactivity. Blood 119 (2) , pp. 368-376. 10.1182/blood-2011-06-360354

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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 antileukemia 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine
Publisher: American Society of Hematology
ISSN: 0006-4971
Last Modified: 13 Nov 2017 23:54

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