针对成熟的单克隆抗体 介素-18 改善小鼠结肠炎,改善表皮屏障功能
Shuji Ikegami1, Keiko Maeda2, Takeshi Urano3,4
1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Inflammatory bowel diseases
|December 23, 2023
概括
一种新型单克隆抗体针对成熟的INTERLEUKIN-18 (IL-18) 有效地治疗炎症性肠病 (IBD) 模型. 这种抗IL-18新表皮质抗体对不对抗TNF-α疗法反应的IBD患者显示出有前途.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 治疗方法 治疗方法
背景情况:
- 抗瘤坏死因子 (TNF) -α抗体用于炎症性肠病 (IBD),但约一半的患者出现治疗耐药性.
- 介素-18 (IL-18) 基因多态性与抗TNF-α疗法的耐药性有关,但IL-18向治疗方法尚未临床上可用.
- 成熟的IL-18蛋白质具有生物活性,这促使研究通过单克隆抗体 (mAb) 针对caspase分裂的成熟IL-18的新表位,作为一种创新的IBD治疗方法,对其进行特定抑制.
研究的目的:
- 为了研究单克隆抗体 (mAb) 的治疗潜力,该抗体准了 caspase 分裂成熟的 Interleukin-18 (IL-18) 的新表位,用于治疗炎症性肠病 (IBD).
- 评估成熟IL-18的特定抑制在改善结肠炎和改善肠道屏障功能和微生物组合中的有效性.
主要方法:
- 在性结肠炎 (UC) 患者中检查了前体和成熟的IL-18表达.
- 在C57/BL6小鼠中诱导大肠炎,使用硫酸 (DSS) 和注射抗IL-18新表位物mAb.
- 分析结肠组织以检测组织学变化,免疫标记物,上皮质透性和肠道微生物组合.
主要成果:
- 在活跃的UC结肠组织中观察到较高的成熟IL-18表达.
- 抗IL-18新表位物mAb治疗改善了DSS诱导的急性和慢性结肠炎,降低了促炎性细胞因子和上皮透性.
- 这种mAb与抗整体IL-18mAb相比显示出更高的疗效,并且在联合治疗中显示出与抗TNF-α治疗的附加效益.
结论:
- 在临床前模型中,抗IL-18新表位物mAb有效地改善了急性和慢性结肠炎.
- 这种新型抗体代表了炎症性肠病 (IBD) 患者的潜在创新治疗策略.
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