期刊
LEUKEMIA
卷 23, 期 7, 页码 1320-1328出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2009.19
关键词
mantle cell lymphoma; cyclin D1; cytotoxic T lymphocytes; dendritic cells; immunotherapy
资金
- University of Texas M.D. Anderson Cancer Center
- National Cancer Institute [R01 CA96569, R01 CA103978]
- Commonwealth Foundation for Cancer Research
- Crutchfield family
- Kimmel family philanthropic foundations
Mantle cell lymphoma (MCL) accounts for 5-10% of all non-Hodgkin lymphomas and has the worst prognosis among all lymphomas. The hallmark of MCL is a t(11;14) translocation that results in overexpression of cyclin D1 by tumor cells of virtually all patients. In this study, we examined whether cyclin D1 could be an effective tumor-associated antigen for immunotherapy. We identified cyclin D1 peptides for HLA-A*0201 and generated peptide-specific CD8(+) T-cell lines from HLA-A*0201(+) blood donors and MCL patients. These cell lines proliferated in response to cyclin D1 peptide-pulsed stimulatory cells. Moreover, the T cells efficiently lysed peptide-pulsed but not unpulsed T2 cells and autologous dendritic cells; cyclin D1(+) and HLA-A*0201(+) human MCL lines MINO, SP53, Jeko-1 and Granta 519; and more importantly, HLA-A*0201(+) primary lymphoma cells from MCL patients. No killing was observed with HLA-A*0201(-) primary lymphoma cells or HLA-A*0201(+) normal blood cells, including B cells. These results indicate that these T cells are potent cytotoxic T cells and recognize cyclin D1 peptides naturally presented by patient lymphoma cells in the context of HLA-A*0201 molecules. Taken together, our work identifies cyclin D1 as a potentially important antigen for immunotherapy of MCL. Leukemia (2009) 23, 1320-1328; doi: 10.1038/leu.2009.19; published online 19 February 2009
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