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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[1][2][3]. | [in vivo]
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].
| Animal Model: | KRASWT and KRASMT CRC xenografts[2] | | Dosage: | 10 mg/kg, together with Irinotecan (HY-16562) (7.5 mg/kg) | | Administration: | Intraperitoneal injection (i.p.), once a week | | Result: | Resulted in tumor regression at day 20. |
| [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. DOI:10.1158/1078-0432.CCR-14-1373
[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. DOI:10.1158/0008-5472.CAN-10-2817
[3] Hoey?T, et al.?DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell?2009;5:168–77. DOI:10.1016/j.stem.2009.05.019
[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. DOI:10.7150/thno.48067 |
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