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埃巴司他单抗,一种新型的白细胞介素 13 受体α1 单克隆抗体,在人体志愿者中以低剂量阻断 STAT6 磷酸化。

Eblasakimab, a novel IL-13 receptor alpha 1 monoclonal antibody, blocks STAT6 phosphorylation with low dose in human volunteers.

机构信息

ASLAN Pharmaceuticals, 400 Concar Drive, San Mateo, CA, USA.

ASLAN Pharmaceuticals, 400 Concar Drive, San Mateo, CA, USA.

出版信息

Clin Immunol. 2023 Aug;253:109677. doi: 10.1016/j.clim.2023.109677. Epub 2023 Jun 12.

Abstract

Eblasakimab is a first-in-class monoclonal antibody under investigation for the treatment of atopic dermatitis (AD), which targets IL-13Rα1, a subunit of the Type 2 receptor complex. IL-13Rα1 stimulates phosphorylation of signal transducer and activator of transcription 6 (STAT6) to drive inflammation. This brief report investigates the mechanistic basis of eblasakimab and its effects on IL-13Rα1 signaling as part of a phase 1a, open-label, single ascending dose study. Single ascending doses of eblasakimab were administered by intravenous or subcutaneous injection to healthy male volunteers. The impact of eblasakimab on IL-13Rα1 receptor occupancy and STAT6 phosphorylation was assessed in participant blood monocytes. No serious treatment emergent adverse events were reported. Eblasakimab effectively blocked the IL-13Rα1 receptor and inhibited STAT6 phosphorylation with single doses of 3 mg/kg intravenously and 300 mg subcutaneously. Results support further clinical development of eblasakimab as a novel biologic for AD, with potential for 2- to 4-week dosing regimens.

摘要

依巴斯单抗是一种研究用于治疗特应性皮炎(AD)的首创类单克隆抗体,其靶向 2 型受体复合物的 IL-13Rα1 亚基。IL-13Rα1 刺激信号转导和转录激活因子 6(STAT6)的磷酸化,以驱动炎症。本简要报告调查了依巴斯单抗的作用机制及其作为 1a 期、开放标签、单次递增剂量研究的一部分对 IL-13Rα1 信号的影响。依巴斯单抗通过静脉或皮下注射给予健康男性志愿者单次递增剂量。在参与者的血液单核细胞中评估依巴斯单抗对 IL-13Rα1 受体占有率和 STAT6 磷酸化的影响。未报告严重的治疗相关不良事件。依巴斯单抗以 3mg/kg 静脉内和 300mg 皮下单次剂量有效阻断 IL-13Rα1 受体并抑制 STAT6 磷酸化。结果支持依巴斯单抗作为 AD 的新型生物制剂的进一步临床开发,具有 2 至 4 周给药方案的潜力。

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