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首页> 外文期刊>Vaccine >The clinical grade maturation cocktail monophosphoryl lipid A plus IFNgamma generates monocyte-derived dendritic cells with the capacity to migrate and induce Th1 polarization
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The clinical grade maturation cocktail monophosphoryl lipid A plus IFNgamma generates monocyte-derived dendritic cells with the capacity to migrate and induce Th1 polarization

机译：临床级成熟鸡尾酒单磷酰脂质A加IFNgamma产生单核细胞衍生的树突状细胞，具有迁移和诱导Th1极化的能力

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摘要

Ex vivo generated monocyte-derived dendritic cells (DCs) are used as a cellular vaccine against cancer in clinical trials. In order to be able to induce an efficient tumour-specific CTL response during immunotherapy, DCs have to be able to migrate to the lymph node and produce the Th1 polarizing cytokine, IL-12p70, upon encounter of T cells in the lymph node. However, most clinically used DCs do not produce IL-12p70 upon T cell contact. In this study, we compared a newly developed clinical grade DC maturation cocktail consisting of MPLA and IFNgamma with two clinically available maturation cocktails, the 'gold standard' (TNFalpha, IL-1beta, IL-6 and PGE(2)) and the 'alpha type 1 polarizing' (TNFalpha, IL-1beta, IFNalpha, IFNgamma and pI:C) cocktail. All three cocktails induced phenotypically mature DCs. However, in contrast to 'gold standard' DCs, which produce no IL-12p70 and as a result induce mainly Th2 cells, DCs matured with MPLA and IFNgamma produce high levels of IL-12p70 upon CD40 triggering. Subsequently, these DCs induce mainly Th1 cells in vitro, even slightly more than by the alpha type 1 polarized DCs. In addition, MPLA plus IFNgamma matured DCs have an intermediate migratory capacity towards CCL21. In conclusion, we here present MPLA plus IFNgamma as a simple clinical grade maturation cocktail to generate immunostimulatory DCs with superior capacity to induce type 1 immunity.
机译：在临床试验中，离体产生的单核细胞衍生的树突状细胞（DC）被用作抗癌的细胞疫苗。为了能够在免疫治疗期间诱导有效的肿瘤特异性CTL反应，DC必须能够在淋巴结中遇到T细胞时迁移到淋巴结并产生Th1极化细胞因子IL-12p70。但是，大多数临床使用的DC在T细胞接触后不会产生IL-12p70。在这项研究中，我们比较了由MPLA和IFNgamma组成的最新开发的临床级DC成熟鸡尾酒与两种临床可用的成熟鸡尾酒“黄金标准”（TNFalpha，IL-1beta，IL-6和PGE（2））和“ α1型极化”（TNFα，IL-1β，IFNα，IFNγ和pI：C）混合物。所有三种鸡尾酒诱导表型成熟的DC。但是，与不产生IL-12p70并因此主要诱导Th2细胞的“金标准” DC相比，在CD40触发后，用MPLA和IFNgamma成熟的DC产生高水平的IL-12p70。随后，这些DC主要在体外诱导Th1细胞，甚至比α1型极化DC诱导的略多。此外，MPLA加γ干扰素成熟的DC对CCL21具有中等迁移能力。总而言之，我们在这里提出MPLA加IFNgamma作为一种简单的临床级成熟鸡尾酒，以产生具有更高的诱导1型免疫力的免疫刺激DC。

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