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Lymphoma

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

Leukemia volume 23, pages 1320–1328 (2009)Cite this article

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 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.

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Acknowledgements

We thank Alison Woo for providing editorial assistance. This work was supported by the institutional start-up funds from The University of Texas M.D. Anderson Cancer Center, National Cancer Institute Grants (R01 CA96569 and R01 CA103978), Commonwealth Foundation for Cancer Research and funds from the Crutchfield family and the Kimmel family philanthropic foundations.

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  1. M Wang and L Sun: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Cancer Medicine, Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    M Wang, L Sun, J Qian, X Han, L Zhang, Z Cai & Q Yi

  2. Division of Pathology and Laboratory Medicine, Department of Hematopathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    P Lin

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Wang, M., Sun, L., Qian, J. et al. Cyclin D1 as a universally expressed mantle cell lymphoma-associated tumor antigen for immunotherapy. Leukemia 23, 1320–1328 (2009). https://doi.org/10.1038/leu.2009.19

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