Bontkes Hetty J, Kramer Duco, Ruizendaal Janneke J, Meijer Chris J L M, Hooijberg Erik
VU University Medical Center, Department of Pathology, Amsterdam, The Netherlands.
Clin Immunol. 2008 Jun;127(3):375-84. doi: 10.1016/j.clim.2008.02.001. Epub 2008 Mar 21.
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 interleukin (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 anti-tumor immune response mediated by CTL and NK effector cells.
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）细胞的免疫疗法对于根除MHC-I阳性和阴性肿瘤可能至关重要。用编码TAA以及促炎细胞因子白细胞介素（IL）-12和IL-18的mRNA转染成熟树突状细胞（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，过表达IL-12的人DC可诱导NK细胞激活增加和效应功能增强，并证实TAA/IL-12双重转染的DC可增加TAA特异性CTL。IL-18转染的作用仅限于表型激活和组织归巢受体的下调，并未增强IL-12对NK细胞效应功能的作用。总之，将TAA和IL-12 mRNA共转染到成熟DC中可提供一种疫苗，用于诱导由CTL和NK效应细胞介导的抗肿瘤免疫反应。
