Suzuki H, Yasukawa K, Saito T, Goitsuka R, Hasegawa A, Ohsugi Y, Taga T, Kishimoto T
Biotechnology Research Laboratory, Tosoh Corporation, Kanagawa, Japan.
Eur J Immunol. 1992 Aug;22(8):1989-93. doi: 10.1002/eji.1830220806.
Myeloma is one of the interleukin (IL)-6-related diseases to which abnormal expression of IL-6 has been reported to be linked. We examined the in vivo inhibitory effect of anti-human IL-6 receptor (IL-6R) antibody on human myeloma cell growth in mice. SCID mice were subcutaneously inoculated with solid tumor of the myeloma cell line S6B45 in which human IL-6 was acting as an autocrine growth factor. Ten intraperitoneal administrations of 100 micrograms of the anti-human IL-6R antibody PM1 at 48-h intervals strongly inhibited the growth of S6B45 cells when the administration started 24 h after tumor inoculation. The tumor growth inhibition in vivo was also observed by administration of the anti-human IL-6 antibody MH166 using the same procedure as for PM1. The inhibitory effect of PM1 was not significant when the administration started 5 or more days after tumor inoculation. This work indicates that anti-human IL-6R antibody, as well as anti-human IL-6 antibody inhibits human myeloma growth in vivo, and provides an animal model for testing the therapeutic value of agents such as antibodies to human IL-6, IL-6R and gp130, an IL-6R-associated signal transducer, in the treatment of human myelomas.
骨髓瘤是白细胞介素（IL）-6相关疾病之一，据报道IL-6的异常表达与之有关。我们研究了抗人IL-6受体（IL-6R）抗体对小鼠体内人骨髓瘤细胞生长的抑制作用。将人IL-6作为自分泌生长因子的骨髓瘤细胞系S6B45的实体瘤皮下接种到重症联合免疫缺陷（SCID）小鼠体内。当在肿瘤接种后24小时开始给药时，每隔48小时腹腔注射100微克抗人IL-6R抗体PM1，共给药10次，可强烈抑制S6B45细胞的生长。采用与PM1相同的给药程序，给予抗人IL-6抗体MH166，也观察到了体内肿瘤生长的抑制作用。当在肿瘤接种后5天或更长时间开始给药时，PM1的抑制作用不显著。这项研究表明，抗人IL-6R抗体以及抗人IL-6抗体在体内均可抑制人骨髓瘤的生长，并为测试诸如抗人IL-6、IL-6R和gp130（一种IL-6R相关信号转导分子）抗体等药物在治疗人骨髓瘤方面的治疗价值提供了一种动物模型。
