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Agonist anti-gp130 transducer monoclonal antibodies are human myeloma cell survival and growth factors

Leukemia volume 14, pages 188–197 (2000)Cite this article

Abstract

We have previously reported obtaining two monoclonal antibodies (mAb) against the human gp130 interleukin-6 (IL-6) transducer which made possible the dimerization of gp130 and the activation of several IL-6-driven functions when used together. We report here that these mAb induce gp130-mediated signaling in human myeloma cells and support the survival and the long-term growth of five IL-6-dependent human myeloma cell lines. Their agonist activity is not affected by neutralizing antibodies to IL-6 or IL-6R. These mAb induce a transient proliferation of primary myeloma cells from most patients with multiple myeloma. Again, IL-6 inhibitors do not affect this agonist activity. By using highly purified primary myeloma cells, we found that these anti-gp130 mAb supported the long-term survival of primary myeloma cells from five patients with primary plasma cell leukemia but failed to induce their long-term growth. For patients with fulminant disease and secondary extramedullary proliferation, the antibodies supported a long-term survival and growth, and anti-gp130 mAb-dependent cell lines were obtained. For patients with medullary involvement only, a co-stimulatory signal is necessary, together with gp130 activation, to trigger cell survival and cycling.

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Acknowledgements

This work was supported by grants from DRC (CHU, Montpellier, France).

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Authors and Affiliations

  1. INSERM U475, Immunopathologie des Maladies Tumorales et Autoimmmunes, Montpellier, France

    Z-J Gu, J De Vos, M Jourdan, X-G Zhang & B Klein

  2. Institute for Molecular Genetics, Montpellier, France

    C Rebouissou

  3. Service des Maladies du Sang, Hôpital Lapeyronie, Montpellier, France

    J-F Rossi

  4. Diaclone, Besançon, Hôpital Saint Eloi, Montepellier, France

    J Wijdenes

  5. Unit for Cellular Therapy, Hôpital Saint Eloi, Montpellier, France

    B Klein

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Gu, ZJ., De Vos, J., Rebouissou, C. et al. Agonist anti-gp130 transducer monoclonal antibodies are human myeloma cell survival and growth factors. Leukemia 14, 188–197 (2000). https://doi.org/10.1038/sj.leu.2401632

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