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The designer cytokine hyper-IL-6 mediates growth inhibition and GM–CSF-dependent rejection of B16 melanoma cells

Oncogene volume 20, pages 972–979 (2001)Cite this article

Abstract

The low immunogenic B16 melanoma cell line was transfected with a mammalian expression vector containing the complementary DNA for a sIL-6R/IL-6 fusion protein, termed Hyper-IL-6 (H-IL-6), which was shown to have biological activities at 100–1000-fold lower concentrations than IL-6 in combination with sIL-6R. The secreted p84 glycoprotein was detected in the supernatant of transfected cells and was fully active on BAF3/gp130 cells, which respond to IL-6/sIL-6R but not to IL-6 alone. Administration of recombinant H-IL-6 to C57BL/6 mice resulted in a prolonged acute phase protein gene expression indicating long systemic persistence of the fusion protein. Transfected B16 cells (B16/H-IL6 cells) showed morphological alterations in combination with a dramatic growth inhibition in vitro. Subcutaneous injection in C57BL/6 mice resulted in an almost complete rejection of B16/H-IL6 cells. This effect was partially abolished in FVB/BL/6 mice transgenic for a GM–CSF receptor antagonist, indicating a GM–CSF-dependent rejection of H-IL-6 transfected B16 cells. These results demonstrate that the anti-tumor effect of cytokines like IL-6 which are secreted by transfected melanoma cells at least in part depends on GM–CSF activity.

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Acknowledgements

This work was supported by grants from the Deutsche Forschungsgemeinschaft (Bonn, Germany), the Stiftung Rheinland Pfalz für Innovation (Mainz, Germany) and the Naturwissenschaftlich-Medizinisches Forschungszentrum (Mainz, Germany).

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Authors and Affiliations

  1. Department of Medicine, Section of Pathophysiology, University of Mainz, Obere Zahlbacher Strasse 63, D-55101 Mainz, Institute of Pathology, University of Cologne, Cologne, Germany

    Suat Özbek, Malte Peters, Kai Breuhahn, Amrit Mann, Manfred Blessing, Martina Fischer & Stefan Rose-John

  2. Department of Cancer Immunology at Great Poland Cancer Center, Poznan, Poland

    Peter Schirmacher & Andrzej Mackiewicz

  3. Department of Biochemistry, Carl-Albrechts-Universität Kiel, Kiel, D-24098, Germany

    Stefan Rose-John

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Özbek, S., Peters, M., Breuhahn, K. et al. The designer cytokine hyper-IL-6 mediates growth inhibition and GM–CSF-dependent rejection of B16 melanoma cells. Oncogene 20, 972–979 (2001). https://doi.org/10.1038/sj.onc.1204180

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