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 ORCID: https://orcid.org/0000-0001-9416-2737, 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

Full text not available from this repository.

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 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:	09 Nov 2022 08:26
URI:	https://orca.cardiff.ac.uk/id/eprint/42800

Citation Data

Cited 18 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item