Lirentelimab

Lirentelimab (AK002) is a humanized IgG1 monoclonal antibody that targets sialic acid-binding Ig-like lectin 8 (SIGLEC8). Lirentelimab induces cell Apoptosis of IL-5-activated eosinophils and inhibits IgE-mediated mast cell activation. Lirentelimab can be used for the research of eosinophilic gastritis and duodenitis[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Inflammation/Immunology

Lirentelimab 的抗原结合片段 (fab) 与重组 SIGLEC8 胞外结构域 (ECD) 的亲和力为 464 pM[1]。 Lirentelimab 对体外表达的 SIGLEC8、嗜酸性粒细胞上表达的 SIGLEC8 以及人血中通过其 Fc 域表达的 NK 细胞具有高亲和力[1]。 Lirentelimab (1 µg/mL) 选择性地结合人外周血中的嗜酸性粒细胞，以及人肺组织中的嗜酸性粒细胞和肥大细胞[1]。 Lirentelimab (0.0001-100 μg/mL；30 min) 诱导 IL-5 激活的嗜酸性粒细胞凋亡[1]。 Lirentelimab (30 min) 对健康供者外周血白细胞 (PBL) 制剂中嗜酸性粒细胞的 EC50 值为 1.9 ng/mL 并产生抗体依赖的细胞毒性 (ADCC)[1]。 Lirentelimab 降低离体人体组织中嗜酸性粒细胞数量[1]。 Apoptosis Analysis[1] Cell Line: Eosinophils Concentration: 10 μg/mL-1 pg/mL Incubation Time: 30 min Result: Dose-dependently induced apoptosis of IL-5-activated (50 ng/mL) eosinophils.

Lirentelimab (100 μg；静脉注射，一次) 在系统性过敏反应小鼠模型中显著抑制 IgE 介导的肥大细胞激活[1]。 Animal Model: Humanized mice (NSG-SGM3) engrafts with human thymus, liver, and HSC[1] Dosage: 100 μg Administration: Intravenous injection; 100 μg, once Result: Completely prevented passive systemic anaphylaxis (PSA) as shown by a lack of change in rectal temperature and symptom scores in mice.

[1]. Youngblood BA, et al. AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice. Int Arch Allergy Immunol. 2019;180(2):91-102.