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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This work was supported by grants from DRC (CHU, Montpellier, France).
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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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DOI: https://doi.org/10.1038/sj.leu.2401632
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