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


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.

SUBMITTER: Chen J 

PROVIDER: S-EPMC4424584 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Chen Jingtao J   Zurawski Gerard G   Zurawski Sandy S   Wang Zhiqing Z   Akagawa Keiko K   Oh Sangkon S   Hideki Ueno U   Fay Joseph J   Banchereau Jacques J   Song Wenru W   Palucka A Karolina AK  

Journal of hematology & oncology 20150414


<h4>Background</h4>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.<h4>Methods</h4>We show here a novel strategy for the development of recombinant vaccines carrying cyclin D1 cancer antigens that can be targete  ...[more]

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