Cyclin D1 as a universally expressed mantle cell lymphoma-associated tumor antigen for immunotherapy

M Wang, L Sun, J Qian, X Han, L Zhang, P Lin, Z Cai… - Leukemia, 2009 - nature.com
M Wang, L Sun, J Qian, X Han, L Zhang, P Lin, Z Cai, Q Yi
Leukemia, 2009nature.com
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 at (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 …
Abstract
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 at (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.
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