Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a microfluidic human 3D co-culture modelCitation formats

  • External authors:
  • Juliane Hübner
  • Marian Raschke
  • Isabel Rütschle
  • Sarah Gräßle
  • Tobias Hasenberg
  • Alexandra Lorenz
  • Susanne Schnurre
  • Roland Lauster
  • Ilka Maschmeyer
  • Thomas Steger-Hartmann
  • Uwe Marx

Standard

Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a microfluidic human 3D co-culture model. / Hübner, Juliane; Raschke, Marian; Rütschle, Isabel; Gräßle, Sarah; Hasenberg, Tobias; Schirrmann, Kerstin; Lorenz, Alexandra; Schnurre, Susanne; Lauster, Roland; Maschmeyer, Ilka; Steger-Hartmann, Thomas; Marx, Uwe.

In: Scientific Reports, Vol. 8, No. 1, 2018, p. 15010.

Research output: Contribution to journalArticle

Harvard

Hübner, J, Raschke, M, Rütschle, I, Gräßle, S, Hasenberg, T, Schirrmann, K, Lorenz, A, Schnurre, S, Lauster, R, Maschmeyer, I, Steger-Hartmann, T & Marx, U 2018, 'Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a microfluidic human 3D co-culture model', Scientific Reports, vol. 8, no. 1, pp. 15010. https://doi.org/10.1038/s41598-018-33462-3

APA

Hübner, J., Raschke, M., Rütschle, I., Gräßle, S., Hasenberg, T., Schirrmann, K., ... Marx, U. (2018). Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a microfluidic human 3D co-culture model. Scientific Reports, 8(1), 15010. https://doi.org/10.1038/s41598-018-33462-3

Vancouver

Author

Hübner, Juliane ; Raschke, Marian ; Rütschle, Isabel ; Gräßle, Sarah ; Hasenberg, Tobias ; Schirrmann, Kerstin ; Lorenz, Alexandra ; Schnurre, Susanne ; Lauster, Roland ; Maschmeyer, Ilka ; Steger-Hartmann, Thomas ; Marx, Uwe. / Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a microfluidic human 3D co-culture model. In: Scientific Reports. 2018 ; Vol. 8, No. 1. pp. 15010.

Bibtex

@article{f75273f7e8ab494581f0aa9a72b7f31f,
title = "Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a microfluidic human 3D co-culture model",
abstract = "Antibody therapies targeting the epithelial growth factor receptor (EGFR) are being increasingly applied in cancer therapy. However, increased tumour containment correlates proportionally with the severity of well-known adverse events in skin. The prediction of the latter is not currently possible in conventional in vitro systems and limited in existing laboratory animal models. Here we established a repeated dose {"}safficacy{"} test assay for the simultaneous generation of safety and efficacy data. Therefore, a commercially available multi-organ chip platform connecting two organ culture compartments was adapted for the microfluidic co-culture of human H292 lung cancer microtissues and human full-thickness skin equivalents. Repeated dose treatment of the anti-EGFR-antibody cetuximab showed an increased pro-apoptotic related gene expression in the tumour microtissues. Simultaneously, proliferative keratinocytes in the basal layer of the skin microtissues were eliminated, demonstrating crucial inhibitory effects on the physiological skin cell turnover. Furthermore, antibody exposure modulated the release of CXCL8 and CXCL10, reflecting the pattern changes seen in antibody-treated patients. The combination of a metastatic tumour environment with a miniaturized healthy organotypic human skin equivalent make this {"}safficacy{"} assay an ideal tool for evaluation of the therapeutic index of EGFR inhibitors and other promising oncology candidates.",
author = "Juliane H{\"u}bner and Marian Raschke and Isabel R{\"u}tschle and Sarah Gr{\"a}{\ss}le and Tobias Hasenberg and Kerstin Schirrmann and Alexandra Lorenz and Susanne Schnurre and Roland Lauster and Ilka Maschmeyer and Thomas Steger-Hartmann and Uwe Marx",
year = "2018",
doi = "10.1038/s41598-018-33462-3",
language = "English",
volume = "8",
pages = "15010",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Springer Nature",
number = "1",

}

RIS

TY - JOUR

T1 - Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a microfluidic human 3D co-culture model

AU - Hübner, Juliane

AU - Raschke, Marian

AU - Rütschle, Isabel

AU - Gräßle, Sarah

AU - Hasenberg, Tobias

AU - Schirrmann, Kerstin

AU - Lorenz, Alexandra

AU - Schnurre, Susanne

AU - Lauster, Roland

AU - Maschmeyer, Ilka

AU - Steger-Hartmann, Thomas

AU - Marx, Uwe

PY - 2018

Y1 - 2018

N2 - Antibody therapies targeting the epithelial growth factor receptor (EGFR) are being increasingly applied in cancer therapy. However, increased tumour containment correlates proportionally with the severity of well-known adverse events in skin. The prediction of the latter is not currently possible in conventional in vitro systems and limited in existing laboratory animal models. Here we established a repeated dose "safficacy" test assay for the simultaneous generation of safety and efficacy data. Therefore, a commercially available multi-organ chip platform connecting two organ culture compartments was adapted for the microfluidic co-culture of human H292 lung cancer microtissues and human full-thickness skin equivalents. Repeated dose treatment of the anti-EGFR-antibody cetuximab showed an increased pro-apoptotic related gene expression in the tumour microtissues. Simultaneously, proliferative keratinocytes in the basal layer of the skin microtissues were eliminated, demonstrating crucial inhibitory effects on the physiological skin cell turnover. Furthermore, antibody exposure modulated the release of CXCL8 and CXCL10, reflecting the pattern changes seen in antibody-treated patients. The combination of a metastatic tumour environment with a miniaturized healthy organotypic human skin equivalent make this "safficacy" assay an ideal tool for evaluation of the therapeutic index of EGFR inhibitors and other promising oncology candidates.

AB - Antibody therapies targeting the epithelial growth factor receptor (EGFR) are being increasingly applied in cancer therapy. However, increased tumour containment correlates proportionally with the severity of well-known adverse events in skin. The prediction of the latter is not currently possible in conventional in vitro systems and limited in existing laboratory animal models. Here we established a repeated dose "safficacy" test assay for the simultaneous generation of safety and efficacy data. Therefore, a commercially available multi-organ chip platform connecting two organ culture compartments was adapted for the microfluidic co-culture of human H292 lung cancer microtissues and human full-thickness skin equivalents. Repeated dose treatment of the anti-EGFR-antibody cetuximab showed an increased pro-apoptotic related gene expression in the tumour microtissues. Simultaneously, proliferative keratinocytes in the basal layer of the skin microtissues were eliminated, demonstrating crucial inhibitory effects on the physiological skin cell turnover. Furthermore, antibody exposure modulated the release of CXCL8 and CXCL10, reflecting the pattern changes seen in antibody-treated patients. The combination of a metastatic tumour environment with a miniaturized healthy organotypic human skin equivalent make this "safficacy" assay an ideal tool for evaluation of the therapeutic index of EGFR inhibitors and other promising oncology candidates.

U2 - 10.1038/s41598-018-33462-3

DO - 10.1038/s41598-018-33462-3

M3 - Article

VL - 8

SP - 15010

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

ER -