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首页> 外文期刊>Vaccine >Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients.
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Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients.

机译：比较用于癌症患者的治疗性单核细胞衍生树突状细胞制剂成熟的α-Type-1极化和标准树突状细胞细胞因子混合物的成熟度。

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The current "gold standard" for generation of dendritic cell (DC) used in DC-based cancer vaccine studies is maturation of monocyte-derived DCs with tumor necrosis factor-alpha (TNF-alpha)/IL-1beta/IL-6 and prostaglandin E(2) (PGE(2)). Recently, a protocol for producing so-called alpha-Type-1 polarized dendritic cells (alphaDC1) in serum-free medium was published based on maturation of monocyte-derived DCs with TNF-alpha/IL-1-beta/polyinosinic:polycytidylic acid (poly-I:C)/interferon (IFN)-alpha and IFN-gamma. This DC maturation cocktail was described to fulfill the criteria for optimal DC generation and to be superior to the standard DC (sDC) cocktail as it induced fully mature DCs with potent IL-12p70 secretion together with CCR7 expression which is necessary for priming of a TH1 response and for migration to the draining lymph node, respectively. In this study, we tested the adaptation of alphaDC1 maturation cocktail to a protocol for clinical grade DC generation from cancer patients performed in X-VIVO 15 medium. We showed that alphaDC1 in this protocol induce lower up-regulation of CD83 and several other maturation markers, co-stimulatory molecules and CCR7 together with higher up-regulation of inhibitory molecules such as PD-L1, ILT2, ILT3 as compared to sDC. Although alphaDC1 matured DCs secreted more IL-12p70 and IL-23 these DCs had lower or similar stimulatory capacity compared to sDCs when used as stimulating cells in mixed lymphocyte reaction (MLR) or for induction of autologous influenza antigen specific T lymphocytes. Thus, our observations underline that alphaDC1 maturation cannot be directly adapted to alternative protocols for DC generation. Also, this study indicates the necessity for further investigation of correlation between in vitro DC parameters and their in vivo efficacy in clinical vaccination trials.
机译：用于基于DC的癌症疫苗研究中的树突状细胞（DC）生成的当前“金标准”是单核细胞衍生DC的成熟与肿瘤坏死因子-α（TNF-alpha）/ IL-1beta / IL-6和前列腺素的结合。 E（2）（PGE（2））。最近，基于单核细胞来源的DC与TNF-α/IL-1-β/多肌苷酸：多胞苷酸的成熟，发表了在无血清培养基中产生所谓的α-Type-1极化树突状细胞（alphaDC1）的协议。 （poly-I：C）/干扰素（IFN）-α和IFN-γ。该DC成熟混合物被描述为满足最佳DC生成的标准，并且优于标准DC（sDC）混合物，因为它诱导了具有有效IL-12p70分泌以及CCR7表达的完全成熟的DC，这对于启动TH1是必需的反应和迁移到引流淋巴结。在这项研究中，我们测试了在X-VIVO 15培养基中从癌症患者产生临床级DC的方案对alphaDC1成熟鸡尾酒的适应性。我们显示，与sDC相比，此协议中的alphaDC1诱导CD83和其他一些成熟标记，共刺激分子和CCR7的较低上调，以及较高的抑制性分子（如PD-L1，ILT2，ILT3）上调。尽管alphaDC1成熟的DC分泌更多的IL-12p70和IL-23，但这些DC在用作混合淋巴细胞反应（MLR）中的刺激细胞或诱导自体流感抗原特异性T淋巴细胞时，与sDC相比具有较低或相似的刺激能力。因此，我们的观察结果强调了alphaDC1成熟不能直接适应DC生成的替代协议。而且，该研究表明在临床疫苗接种试验中进一步研究体外DC参数与其体内功效之间的相关性的必要性。

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