Abstract
BackgroundMantle 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.MethodsWe 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.ResultsHealthy 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0131-7) contains supplementary material, which is available to authorized users.
Highlights
Mantle cell lymphoma (MCL) is a distinct clinical subtype of B cell non-Hodgkin’s lymphoma (NHL) and accounts for approximately 5%–10% of all lymphoma cases
We have investigated specific T cell responses to the whole cyclin D1 protein, focusing on identifying potential dominant T cell epitopes. We found that both healthy individuals and MCL patients have a broad repertoire of cyclin D1-specific T cells supporting the utility of cyclin D1 as a tumor antigen for immunotherapy
We have developed a novel vaccine based on targeting cyclin D1 to dendritic cells (DCs) via the human DC surface receptor CD40 and explore the immune responses generated by this novel vaccine
Summary
Mantle cell lymphoma (MCL) is a distinct clinical subtype of B cell non-Hodgkin’s lymphoma (NHL) and accounts for approximately 5%–10% of all lymphoma cases. Current treatment is based on standard chemotherapy often combined with monoclonal antibody rituximab, followed by hematopoietic stem cell transplantation [1,2,3]. These treatment regimens can induce a high rate of remission, most patients relapse and cannot be cured [4,5]. Mantle cell lymphoma (MCL) is a distinct clinical pathologic subtype of B cell non-Hodgkin’s lymphoma often associated with poor prognosis. MCL is associated with overexpression of cyclin D1 rendering this molecule an interesting target for immunotherapy
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