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

作者：Chen, Jingtao^*; Zurawski, Gerard; Zurawski, Sandy; Wang, Zhiqing; Akagawa, Keiko; Oh, Sangkon; Hideki, Ueno; Fay, Joseph; Banchereau, Jacques; Song, Wenru; Palucka, A. Karolina

来源：Journal of Hematology & Oncology, 2015, 8(1): 35.

DOI：10.1186/s13045-015-0131-7

• Mantle cell lymphoma
• Cyclin D1
• Vaccine
• Dendritic cells
• Tumor antigen

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-gamma. 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.

• 出版日期2015-4-14
• 单位吉林大学