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Targeting cyclin D1 for mantle cell lymphoma

Cyclin D1, an important component of cell cycle and a protein with known oncogenic potential, is over expressed in mantle cell lymphoma (MCL). MCL is a distinct clinical pathologic subtype of B cell non-Hodgkin's lymphoma often associated with poor prognosis. New therapeutic approaches based on boosting anti-tumor immunity are being developed. Targeting cyclin D1 for MCL is rendering an interesting target for immunotherapy. However, the knowledge on the frequency and profile of cyclin D1-specific T cells in MCL patients is fragmented. Here we show that both healthy individuals and MCL patients have a broad repertoire of cyclin D1-specific CD4+ and CD8+ T cells covering numerous epitopes from the whole cyclin D1 protein. Cyclin D1-specific T cells secrete IFN-g and type 2 cytokines including IL-5 and IL-13. Additionally, DCs loaded with whole tumor cells or with selected peptides can elicit cyclin D1-specific CD8+ T cells that kill MCL tumors. Furthermore, a recombinant vaccine based on targeting cyclin D1 antigen to human DCs via an anti-CD40 mAb was developed. Targeting monocyte-derived human DCs in vitro with anti-CD40-cyclin D1 fusion protein expanded a broad repertoire of cyclin D1-specific CD4+ and CD8+ T cells. Therefore, cyclin D1 represents a good target for immunotherapy.

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Correspondence to Jingtao Chen.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Keywords

  • Peptide
  • Lymphoma
  • Fusion Protein
  • Mantle Cell Lymphoma
  • Good Target