Chen Jingtao, Zurawski Gerard, Zurawski Sandy, Wang Zhiqing, Akagawa Keiko, Oh Sangkon, Hideki Ueno, Fay Joseph, Banchereau Jacques, Song Wenru, Palucka A Karolina
Institute of Translational Medicine, the First Hospital, Jilin University, Changchun, 130031, China.
Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA.
J Hematol Oncol. 2015 Apr 14;8:35. doi: 10.1186/s13045-015-0131-7.
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.
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.
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.
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.
套细胞淋巴瘤（MCL）是B细胞非霍奇金淋巴瘤的一种独特临床病理亚型，常与不良预后相关。需要基于增强抗肿瘤免疫力的新治疗方法。MCL与细胞周期蛋白D1的过表达相关，因此使该分子成为免疫治疗的一个有吸引力的靶点。
我们在此展示了一种开发携带细胞周期蛋白D1癌症抗原的重组疫苗的新策略，该疫苗可通过CD40靶向树突状细胞（DCs）。
健康个体和MCL患者拥有广泛的细胞周期蛋白D1特异性CD4(+)和CD8(+) T细胞库。细胞周期蛋白D1特异性T细胞分泌干扰素-γ。负载全肿瘤细胞或选定肽的DCs可引发杀死MCL肿瘤细胞的细胞周期蛋白D1特异性CD8(+) T细胞。我们开发了一种基于通过抗CD40单克隆抗体将细胞周期蛋白D1抗原靶向人DCs的重组疫苗。用抗CD40-细胞周期蛋白D1融合蛋白在体外靶向单核细胞衍生的人DCs可扩增广泛的细胞周期蛋白D1特异性CD4(+)和CD8(+) T细胞库。
本研究表明细胞周期蛋白D1是免疫治疗的一个良好靶点，将细胞周期蛋白D1靶向DCs为套细胞淋巴瘤疫苗提供了一种新策略。
