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Mouse Anti-human Interleukin-6 Receptor Monoclonal Antibody Inhibits Proliferation of Fresh Human Myeloma Cells in vitro
Authors:Hideo Goto  Chihiro Shimazaki  Tetsuya Tatsumi  Noboru Yamagata  Toshiyuki Hirata  Eishi Ashihara  Naritoshi Oku  Tohru Inaba  Naohisa Fujita  Yasuo Koishihara  Yoshiyuki Ohsugi  Masao Nakagawa
Institution:Second Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602;Department of Laboratory Medicine, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602;Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Company, 1-135 Komakado, Gotemba, Shizuoka 412
Abstract: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 / μ /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.
Keywords:Multiple myeloma  IL-6  Anti-IL-6 receptor antibody  Anti-IL-6 antibody
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