Mouse anti-human interleukin-6 receptor monoclonal antibody inhibits proliferation of fresh human myeloma cells in vitro.
Interleukin-6 (IL-6) is a major growth factor in multiple myeloma. We investigated the effect of mouse anti-human IL-6 receptor monoclonal antibody (anti-IL-6R mAb) on the in vitro proliferation of freshly isolated myeloma cells from 21 patients to evaluate the therapeutic potential. The addition of anti-IL-6R mAb inhibited more than 30% of the spontaneous proliferation of myeloma cells in 9 of 21 cases in a dose- (0.1 to 20 micrograms/ml) and time-dependent manner. The inhibitory effects of anti-IL-6R mAb did not differ significantly from that of anti-IL-6 mAb, and were correlated with the extent of the response of myeloma cells to IL-6. Flow cytometric analysis showed that all myeloma cells expressed IL-6R, whose intensity was not correlated with either the extent of response of myeloma cells to IL-6 or the inhibitory effects of anti-IL-6R mAb on proliferation of myeloma cells. Although our study showed heterogeneity in the proliferative responses of myeloma cells to IL-6 and anti-IL-6R mAb, these observations suggest the possibility of using anti-IL-6R mAbs for treating some patients with multiple myeloma whose growth depends on IL-6.
Goto
H
H
Second Department of Medicine, Kyoto Prefectural University of Medicine.
Shimazaki
C
C
Tatsumi
T
T
Yamagata
N
N
Hirata
T
T
Ashihara
E
E
Oku
N
N
Inaba
T
T
Fujita
N
N
Koishihara
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal; D002455:Cell Division; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D006131:Growth Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000494:pharmacology; D007952:Leukemia, Plasma Cell / Q000473:pathology*; D051379:Mice; D009101:Multiple Myeloma / Q000473:pathology*; D018123:Receptors, Interleukin / Q000502:physiology*; D019947:Receptors, Interleukin-6; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D006131:Growth Inhibitors; D015850:Interleukin-6; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6