Tumor associated antigen and interleukin-12 mRNA transfected dendritic cells enhance effector function of natural killer cells and antigen specific T-cells
Tumor associated antigen and interleukin-12 mRNA transfected dendritic cells enhance effector function of natural killer cells and antigen specific T-cells
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DOI：
10.1016/j.clim.2008.02.001
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发表时间：
2008-06-01
影响因子：
8.6
通讯作者：
Hooijberg, Erik
中科院分区：
文献类型：
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作者：
Bontkes, Hetty J.;Kramer, Duco;Hooijberg, Erik
旨在联合激活肿瘤相关抗原 (TAA) 特异性细胞毒性 T 淋巴细胞 (CTL) 和自然杀伤 (NK) 细胞的免疫疗法可能对于根除 MHC-I 阳性和阴性肿瘤至关重要。用编码 TAA 和促炎细胞因子白细胞介素 (IL)-12 和 IL-18 的 mRNA 转染的成熟树突状细胞 (DC) 进行疫苗接种可能会增加 NK 细胞和 TAA 特异性 CTL 活性。我们在此证明IL-12过表达的人DC可诱导NK细胞活化和效应子功能增加，并证实TAA/IL-12双转染的DC增加了TAA特异性CTL。 IL-18转染的作用仅限于组织归巢受体的表型激活和下调，并且不会增加IL-12对NK细胞效应器功能的影响。总之，将 TAA 和 IL-12 mRNA 共转染到成熟 DC 中提供了一种用于诱导由 CTL 和 NK 效应细胞介导的抗肿瘤免疫应答的疫苗。 (c) 2008 Elsevier Inc. 保留所有权利。
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.