Blood. 2012 Jan 12;119(2):368-76. Epub 2011 Oct 24.

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

Nagai K, Ochi T, Fujiwara H, An J, Shirakata T, Mineno J, Kuzushima K, Shiku H, Melenhorst JJ, Gostick E, Price DA, Ishii E, Yasukawa M.

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Department of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Japan.

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 AURKA(207-215)-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, AURKA(207-215)-specific TCR-transduced CD4(+) T cells displayed target-responsive Th1 cytokine production. Finally, AURKA(207-215)-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.

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Blood. 2012 Jan 12;119(2):322-3.

PMID:: 22025529; [PubMed - indexed for MEDLINE]

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Anti-Aurora A antibody [35C1] ab13824 - Abcam plc

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