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.
Seribantumab (0.1 nmol/L-10 μmol/L; 96 h) dose-dependently inhibits two cell lines that harbor NRG1 rearrangements (MDA-MB-175-VII, DOC4-NRG1 fusion and LUAD-0061AS3, SLC3A2-NRG1 fusion) with IC50 values of 0.02, 1.4, 45.2 and 203 μmol/L for MDA-MB-175-VII, LUAD-0061AS3, MCF-7 and HBECp53 cells, respectively[1].Seribantumab (0.1, 1, and 10 μmol/L; 24-48 h) effectively inhibits growth of tumor cell lines that harbor NRG1 fusions or NRG1 amplification[1].Seribantumab (0-0.5 μmol/L; 96 h) largely suppresses growth of NRG1-b1-stimulated MCF-7 cells[1].Seribantumab (0-10 μmol/L; 48 h) induces apoptosis of cells harboring NRG1 rearrangements[1].Seribantumab (0-10 μmol/L; 1 h) inhibits phosphorylation of downstream mediators in cells with NRG1 alterations[1].
Seribantumab (0.6-1 mg; i.p. twice weekly for once) reduces tumor growth in non-small cell lung cancer (NSCLC) patient-derived xenograft (PDX) mice model with a higher efficacy than afatinib, blocks phosphorylation of growth modulators and induces expression of apoptosis markers in vivo[1].Seribantumab (1-10 mg; i.p. twice weekly for once) eliminates the vast majority of tumor cells and causes no significant change in overall animal health or weight in High-grade serous ovarian cancer (HGSOC) mice model[1].
References:
[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.