Tumor associated antigen and interleukin-12 mRNA transfected dendritic cells enhance effector function of natural killer cells and antigen specific T-cells

被引:56
作者
Bontkes, Hetty J. [1 ]
Kramer, Duco [1 ]
Ruizendaal, Janneke J. [1 ]
Meijer, Chris J. L. M. [1 ]
Hooijberg, Erik [1 ]
机构
[1] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands
关键词
human; dendritic cells; natural killer cells; cytokines; vaccination;
D O I
10.1016/j.clim.2008.02.001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immunotherapy aiming at the combined activation of tumor associated antigen (TAA) specific cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells may be crucial to eradicate both MHC-I positive and negative tumors. Vaccination with mature dendritic cells (DC) transfected with mRNA encoding for TAA and the pro-inflammatory cytokines interteukin (IL)-12 and IL-18 may increase NK cell and TAA specific CTL activity. We demonstrate here that IL-12 over-expressing human DC induces increased NK cell activation and effector function and confirm the increase in TAA specific CTL by TAA/IL-12 double transfected DC. The effects of IL-18 transfection were limited to phenotypic activation and down-regulation of tissue homing receptors and did not add to the effect of IL-12 on NK cell effector function. In conclusion, co-transfection of TAA and IL-12 mRNA into mature DCs offers a vaccine for the induction of an antitumor immune response mediated by CTL and NK effector cells. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:375 / 384
页数:10
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