Investigational New Drugs

, 27:579

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

  • Setsuo Hasegawa
  • Hideaki Kato
  • Hiroki Yamaguchi
  • Masafumi Yohda
  • Kazuhiko Obara
  • Hiroshi Izutsu
  • Mieko Ogura
  • Masato Mitsuhashi
SHORT REPORT

DOI: 10.1007/s10637-009-9223-y

Cite this article as:
Hasegawa, S., Kato, H., Yamaguchi, H. et al. Invest New Drugs (2009) 27: 579. doi:10.1007/s10637-009-9223-y
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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.

Keywords

TrastuzumabAntibody medicineInflammatory cytokinemRNA expressionCCL20IL8

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Setsuo Hasegawa
    • 1
  • Hideaki Kato
    • 1
  • Hiroki Yamaguchi
    • 2
  • Masafumi Yohda
    • 3
  • Kazuhiko Obara
    • 4
  • Hiroshi Izutsu
    • 4
  • Mieko Ogura
    • 5
  • Masato Mitsuhashi
    • 5
  1. 1.Sekino Clinical Pharmacology ClinicTokyoJapan
  2. 2.Department of 3rd Internal Medicine (Hematology & Oncology)Nippon Medical SchoolTokyoJapan
  3. 3.Department of Biotechnology and Life Science, Graduate School of TechnologyTokyo University of Agriculture and TechnologyTokyoJapan
  4. 4.Hitachi Chemical Co., Ltd.HitachiJapan
  5. 5.Hitachi Chemical Research Center, Inc.IrvineUSA