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

Leukemia. 2000 Jan;14(1):188-97. doi: 10.1038/sj.leu.2401632.

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. Leukemia (2000) 14, 188-197.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antigens, CD / immunology*
  • Blotting, Western
  • Cell Division
  • Cell Survival / immunology
  • Cytokine Receptor gp130
  • Flow Cytometry
  • Growth Substances / physiology*
  • Humans
  • Membrane Glycoproteins / immunology*
  • Middle Aged
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology*
  • Signal Transduction*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Growth Substances
  • IL6ST protein, human
  • Membrane Glycoproteins
  • Cytokine Receptor gp130