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首页> 外文期刊>Cytokine >Comparative activity of Sant7 and anti-IL-6, IL-6R monoclonal antibodies in a murine model of B-cell lymphoma.
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Comparative activity of Sant7 and anti-IL-6, IL-6R monoclonal antibodies in a murine model of B-cell lymphoma.

机译：Sant7和抗IL-6，IL-6R单克隆抗体在B细胞淋巴瘤小鼠模型中的比较活性。

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摘要

Interleukin-6 (IL-6) plays a central role in the pathogenesis of several autoimmune and inflammatory diseases as well as B-cell lymphoproliferative disorders. This work describes the effects of the recombinant or adenovirally-delivered IL-6 superantagonist Sant7, anti-IL-6 and IL-6 receptor monoclonal antibodies in a severe murine model of human B-cell lymphoma induced in SCID mice by transplantation of an LCL-41 cell line variant (isotype-switched IgM>IgG). Survival of 60% of the animals treated with anti-gp130 was observed up to day 33, while about 20% of the animals survived with anti-gp80 and Sant7 treatment. No survival was observed with the anti-IL-6 monoclonal antibody treatment. No significant change in serum and peritoneal levels of human IL-6 (hIL-6) and soluble human IL-6 receptor (shIL-6R) was observed in the recombinant Sant7-treated group towards the control group. The anti-gp80 monoclonal antibody induced significant increase of both hIL-6R and hIL-6 in serum and peritoneum. The anti-gp130 monoclonal antibody treatment determined a reduction of the seric shIL-6R and a significant increase of the seric hIL-6. Anti-IL-6 monoclonal antibody administration resulted in a reduction of serum and in an increase of peritoneal hIL-6. Treatment with adenoviral Sant7 was associated with a reduction of circulating shIL-6R, hIgG and mSAP. However, only marginal anti-tumor efficacy of the adenoviral Sant7 was observed. Overall, the present data suggest a potential for anti-hIL-6 therapy in B-cell lymphomas. Less severe animal models might be useful to better evaluate Sant7 efficacy alone or in combination with other anti-IL-6 therapeutics.
机译：白介素-6（IL-6）在几种自身免疫性疾病和炎性疾病以及B细胞淋巴组织增生性疾病的发病机理中起着核心作用。这项工作描述了重组或腺病毒递送的IL-6超拮抗剂Sant7，抗IL-6和IL-6受体单克隆抗体在SCID小鼠通过LCL移植诱导的人B细胞淋巴瘤严重鼠模型中的作用-41细胞系变体（同种型转换的IgM> IgG）。直至第33天，观察到60％用抗gp130处理的动物的存活，而约20％的动物用抗gp80和Sant7处理存活。用抗IL-6单克隆抗体治疗未观察到存活。在重组Sant7治疗组中，相对于对照组，人IL-6（hIL-6）和可溶性人IL-6受体（shIL-6R）的血清和腹膜水平没有显着变化。抗gp80单克隆抗体诱导血清和腹膜中hIL-6R和hIL-6的显着增加。抗gp130单克隆抗体治疗确定了血清shIL-6R的减少和血清hIL-6的显着增加。抗IL-6单克隆抗体的施用导致血清的减少和腹膜hIL-6的增加。腺病毒Sant7的治疗与循环shIL-6R，hIgG和mSAP的减少有关。但是，仅观察到腺病毒Sant7的边缘抗肿瘤功效。总的来说，目前的数据表明在B细胞淋巴瘤中进行抗hIL-6治疗的潜力。较轻的动物模型可能有助于更好地单独或与其他抗IL-6治疗剂联合评估Sant7疗效。

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