Journal
BLOOD
Volume 119, Issue 2, Pages 368-376Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-06-360354
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Health, Labor and Welfare
- Third Term Comprehensive Control Research for Cancer
- Grants-in-Aid for Scientific Research [21591245, 24591426, 23659489, 23591419, 24390245] Funding Source: KAKEN
- Medical Research Council [G0501963] Funding Source: researchfish
- MRC [G0501963] Funding Source: UKRI
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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 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. (Blood. 2012;119(2):368-376)
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