Demcizumab (OMP 21M18) is an anti-DLL4 monoclonal antibody. Demcizumab is a potent inhibitor of the Notch pathway. Demcizumab alone or in combination with chemotherapy is effective in various cancer models.
Demcizumab (0-100 μg/mL) binds to human DLL4 but not murine DLL4, and blocks DLL4 binding to Notch1 receptor in a FACS-binding assay[3].Demcizumab (20 μg/mL, 48 h) reduces HES1 and DTX1 mRNA expression in PDTALL cells[4].Demcizumab (0-80 μg/mL, 1 or 2 or 3 days) promotes cell death and early apoptosis in PDTALL13 cells[4].
Demcizumab (10 mg/kg, i.p., once a week) together with Irinotecan (7.5 mg/kg) show a significant antitumor effect in KRASWT and KRASMT CRC xenografts[2].Demcizumab is efficacious alone or in combination with Irinotecan (7.5 mg/kg) in OMP-C8 colon tumors[3].Demcizumab (20 mg/kg/week, i.p.) increases mice survival in irradiated NRG mice injected PDTALL13 cells[4].
References:
[1]. Smith DC, et al. A phase I dose escalation and expansion study of the anticancer stem cell agent demcizumab (anti-DLL4) in patients with previously treated solid tumors. Clin Cancer Res. 2014 Dec 15;20(24):6295-303.
[2]. Fischer M, et al. Anti-DLL4 inhibits growth and reduces tumor-initiating cell frequency in colorectal tumors with oncogenic KRAS mutations. Cancer Res 2011;71:1520-5.
[3]. Hoey T, et al. DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell 2009;5:168–77.
[4]. Xiong H, et al. Spleen plays a major role in DLL4-driven acute T-cell lymphoblastic leukemia. Theranostics. 2021 Jan 1;11(4):1594-1608.