Abstract
Background: Mantle cell lymphoma (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 needed. MCL is associated with overexpression of cyclin D1 thus rendering this molecule an interesting target for immunotherapy. Methods: We show here a novel strategy for the development of recombinant vaccines carrying cyclin D1 cancer antigens that can be targeted to dendritic cells (DCs) via CD40. Results: Healthy individuals and MCL patients have a broad repertoire of cyclin D1-specific CD4+ and CD8+ T cells. Cyclin D1-specific T cells secrete IFN-γ. DCs loaded with whole tumor cells or with selected peptides can elicit cyclin D1-specific CD8+ T cells that kill MCL tumor cells. We developed a recombinant vaccine based on targeting cyclin D1 antigen to human DCs via an anti-CD40 mAb. 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. Conclusions: This study demonstrated that cyclin D1 represents a good target for immunotherapy and targeting cyclin D1 to DCs provides a new strategy for mantle cell lymphoma vaccine.
Original language | English (US) |
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Article number | 35 |
Journal | Journal of Hematology and Oncology |
Volume | 8 |
Issue number | 1 |
DOIs | |
State | Published - Apr 14 2015 |
Keywords
- Cyclin D1
- Dendritic cells
- Mantle cell lymphoma
- Tumor antigen
- Vaccine
ASJC Scopus subject areas
- Molecular Biology
- Hematology
- Oncology
- Cancer Research