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

We have previously reported obtaining two monoclonal antibodies (mAb) again st the human gp130 interleukin-6 (IL-6) transducer which made possible the dimerization of gp130 and the activation of several IL-6-driven functions w hen used together. We report here that these mAb induce gp130-mediated sign aling in human myeloma cells and support the survival and the long-term gro wth 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 ind uce a transient proliferation of primary myeloma cells from most patients w ith multiple myeloma, Again, IL-6 inhibitors do not affect this agonist act ivity. By using highly purified primary myeloma cells, we found that these anti-gp130 mAb supported the long-term survival of primary myeloma cells fr om five patients with primary plasma cell leukemia but failed to induce the ir long-term growth. For patients with fulminant disease and secondary extr amedullary proliferation, the antibodies supported a long-term survival and growth, and anti-gp130 mAb-dependent cell lines were obtained. For patient s with medullary involvement only, a co-stimulatory signal is necessary, to gether with gp130 activation, to trigger cell survival and cycling.