Seribantumab

Seribantumab (MM 121) is a fully human IgG2 monoclonal antibody that targets HER3. Seribantumab blocks the activation of epidermal growth factor receptor (ErbB) family members and its downstream signal. Seribantumab inhibits neuregulin 1 (NRG1) fusion-dependent tumorigenesis in vitro and in vivo in breast, lung and ovarian patient-derived cancer models[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

Seribantumab (0.1 nmol/L-10 μmol/L; 96 h) 剂量依赖性地抑制两种神经调节蛋白 1 (NRG1) 重排的融合细胞系 (MDA-MB-175-VII、DOC4-NRG1 融合和 LUAD-0061AS3、SLC3A2-NRG1 融合)，抑制 MDA-MB-175-VII、LUAD-0061AS3、MCF-7 和 HBECp53 细胞的 IC50 值分别为 0.02、1.4、45.2 和 203 μmol/L[1]。 Seribantumab (0.1, 1 and 10 μmol/L; 24-48 h) 有效抑制 NRG1 融合或 NRG1 扩增的肿瘤细胞系的生长[1]。 Seribantumab (0-0.5 μmol/L; 96 h) 强烈抑制 NRG1-b1 刺激的 MCF-7 细胞的生长[1]。 Seribantumab (0-10 μmol/L; 48 h) 诱导 NRG1 重排细胞的凋亡[1]。 Seribantumab (0-10 μmol/L; 1 h) 抑制 NRG1 下游调节因子的磷酸化[1]。 Apoptosis Analysis[1] Cell Line: MDA-MB-175-VII and LUAD-0061AS3 cell lines Concentration: 0-10 μmol/L Incubation Time: 48 hours Result: Dose-dependently increased caspase 3/7 activity and induced apoptosis of NRG1 fusion-positive breast and lung cancer cell lines. Western Blot Analysis[1] Cell Line: LUAD-0061AS3 and HBECp53-CD74-NRG1 cell lines Concentration: 0, 0.001, 0.01, 0.1, 1 and 10 μmol/L Incubation Time: 1 hour Result: Inhibited the phosphorylation of EGFR, HER2, HER3, HER4, AKT and STAT3 in LUAD-0061AS3 cells. Completely inhibited HER3, AKT, p70S6K and STAT3, and reduced phosphorylation of HER2, EGFR and HER4 to a lesser extent in HBECp53-CD74-NRG1 cells.

Seribantumab (0.6-1 mg；腹腔注射，两周一次，共注射一次) 比阿法替尼更有效地减少非小细胞肺癌肿瘤生长，阻断生长调节因子的磷酸化并诱导细胞凋亡标志物的表达[1]。 Seribantumab (1-10 mg；腹腔注射，两周一次，共注射一次) 在高级别浆液性卵巢癌 (HGSOC) 小鼠模型中，可以消除绝大多数肿瘤细胞，并且对动物健康或体重没有显著变化[1]。 Animal Model: Immunocompromised mice with LUAD-0061AS3 PDX tumors implanted[1] Dosage: 0.6, 0.75 and 1 mg Administration: Intraperitoneal injection; 0.6, 0.75 and 1 mg for once Result: Effectively reduced tumor growth of mice and time- and dose-dependently reduced phosphorylation of HER2, HER3, AKT, and ERK1/2. Induced the expression if proapoptotic protein, BIM.

[1]. Odintsov I, et al. The Anti-HER3 mAb Seribantumab Effectively Inhibits Growth of Patient-Derived and Isogenic Cell Line and Xenograft Models with Oncogenic NRG1 Fusions. Clin Cancer Res. 2021 Jun 1;27(11):3154-3166.