A novel vaccine for mantle cell lymphoma based on targeting cyclin D1 to dendritic cells via CD40

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.

Follicular dendritic cell tumour/sarcoma: a commonly misdiagnosed tumour in the thorax

“…published a study recently on a novel vaccine for mantle cell lymphoma targeting cyclin D1 while Dragnev et al . focused on its role as adjuvant in the treatment of aerodigestive tract tumours . To our knowledge, our results are novel regarding cyclin D1 expression in FDCS and its presence should be considered further as both a supportive diagnostic marker and potential therapeutic target in FDCS.…”

Mantle cell lymphoma in the era of precision medicine-diagnosis, biomarkers and therapeutic agents

“…The overall beneficial effect was potentiated by co-administration of rituximab [213]. Chen et al, 2015 have developed a novel vaccine based on targeting Cyclin D1 to Dendritic cells (DC) via the human DC surface receptor CD40 to elicit Cyclin D1-specific T cells, which is being tested in in vivo models [214]. Newer clinical trials have been designed to evaluate the clinical efficiency of some of these novel antibodies and vaccines (Table 3).…”

Drug discovery and therapeutic delivery for the treatment of B and T cell tumors

“…With the proper antigen presentation to cytotoxic T cells, cancer cells can be targeted similarly to old or virally infected cells. Cyclin D1, a frequently upregulated cyclin in mantle cell lymphoma has been singled out as an effective antigen for vaccination therapy 163 . The frequent over expression of cyclin D1 in mantle cell lymphoma and its potency in T cell activation upon cross presentation contribute to why cyclin D1 makes an excellent target for vaccines 163 .…”

“…Cyclin D1, a frequently upregulated cyclin in mantle cell lymphoma has been singled out as an effective antigen for vaccination therapy 163 . The frequent over expression of cyclin D1 in mantle cell lymphoma and its potency in T cell activation upon cross presentation contribute to why cyclin D1 makes an excellent target for vaccines 163 . Along other lines, Mattarollo et al showed that a cancer antigen cocktail with an α–galactosylceramide (α-GalCer) adjuvant could successfully activate natural killer T cells against B cell lymphoma and subsequently inhibit its growth in mice lymphoma models 164 .…”