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

Summary

Heparinized human whole blood from 16 adult volunteers was stimulated with achievable blood concentrations of trastuzumab and rituximab at 37°C for 4 h, then CCL20, IL8, and β-actin mRNA were quantified. The fold increase of β-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 μg/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.

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Acknowledgments

We would like to thank Ms. Ai Kobayashi and Ms. Sayaka Kimura (Sekino Clinical Pharmacology Clinic) for technical assistant during blood collection and stimulations, Dr. Jifan Li, Mr. Taku Murakami, and Mr. Toshit Sen (Hitachi Chemical Research Center) for technical assistant during HPLC analyses, and Dr. Terumasa Miyamoto (professor emeritus, Tokyo University) for his critical review of the manuscript.

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Correspondence to Masato Mitsuhashi.

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Hasegawa, S., Kato, H., Yamaguchi, H. et al. Trastuzumab-induced CCL20 and interleukin-8 mRNA in human whole blood ex vivo . Invest New Drugs 27, 579 (2009). https://doi.org/10.1007/s10637-009-9223-y

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Keywords

  • Trastuzumab
  • Antibody medicine
  • Inflammatory cytokine
  • mRNA expression
  • CCL20
  • IL8