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Trastuzumab-induced CCL20 and interleukin-8 mRNA in human whole blood ex vivo

机译:曲妥珠单抗诱导人全血中CCL20和白细胞介素8 mRNA表达

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摘要

Heparinized human whole blood from 16 adult volunteers was stimulated with achievable blood concentrations of trastuzumab and rituximab at 37degC for 4 h, then CCL20, IL8, and beta-actin mRNA were quantified. The fold increase of (3-actin was all less than 1.5, and heat aggregated IgG induced both IL8 and CCL20 mRNA in all cases, suggesting that the assay was performed appropriately. Rituximab reduced the levels of CCL20 mRNA in approximately 1/3 of subjects, whereas 50 mug/ml trastuzumab induced IL8 and CCL20 mRNA in more than half of subjects. Although the results do not directly indicate the toxicity of antibody medicines, the individual variation found under physiological ex vivo condition will be an interesting clinical research model for drug safety analysis.
机译:用可达到的血药曲妥珠单抗和利妥昔单抗在37℃下刺激来自16名成年志愿者的肝素化的人类全血4小时,然后定量CCL20,IL8和β-肌动蛋白mRNA。 (3-肌动蛋白的增加倍数均小于1.5,并且热聚集的IgG均在所有情况下均诱导IL8和CCL20 mRNA的表达,这表明该测定是适当的。利妥昔单抗降低了约1/3受试者的CCL20 mRNA水平,而50杯/毫升的曲妥珠单抗可在一半以上的受试者中诱导IL8和CCL20 mRNA的表达,尽管结果并未直接表明抗体药物的毒性,但在生理离体条件下发现的个体差异将成为该药物有趣的临床研究模型安全分析。

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