Agonist anti-gp130 transducer monoclonal antibodies are human myeloma cell survival and growth factors.
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.
Gu
Z J
ZJ
INSERM U475, Immunopathologie des Maladies Tumorales et Autoimmmunes, Montpellier, France.
De Vos
J
J
Rebouissou
C
C
Jourdan
M
M
Zhang
X G
XG
Rossi
J F
JF
Wijdenes
J
J
Klein
B
B
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D015153:Blotting, Western; D002455:Cell Division; D002470:Cell Survival / Q000276:immunology; D050822:Cytokine Receptor gp130; D005434:Flow Cytometry; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006133:Growth Substances; C494199:IL6ST protein, human; D008562:Membrane Glycoproteins; D050822:Cytokine Receptor gp130