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Z-J Gu1, J De Vos1, C Rebouissou2, M Jourdan1, X-G Zhang1, J-F Rossi3, J Wijdenes4 & B Klein1,5
1INSERM U475, Immunopathologie des Maladies Tumorales et Autoimmmunes, Montpellier, France
2Institute for Molecular Genetics, Montpellier, France
3Service des Maladies du Sang, Hôpital Lapeyronie, Montpellier, France
4Diaclone, Besançon, Hôpital Saint Eloi, Montepellier, France
5Unit for Cellular Therapy, Hôpital Saint Eloi, Montpellier, France
Correspondence to: B Klein, INSERM U475, 99 Rue Puech Villa, 34197 Montpellier Cedex 5, France; Fax: 33–(0)4–67–04–18–63
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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.
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