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Brontictuzumab (OMP 52M51) is a monoclonal antibody (MAb) that inhibits Notch1 signal. Brontictuzumab selectively binds the negative regulatory region of the Notch1. Brontictuzumab inhibits tumor cell proliferation. Brontictuzumab can be used in the research of leukemia and lymphoma[1][2][3]. | [in vivo]
Brontictuzumab (15 mg/kg, i.p.) reduces tumor burden in T-ALL xenograft[3].
Brontictuzumab (20 mg/kg, i.p., every 4?days) inhibits DLL4 induced activation of Notch1 in MCL model[2].
| Animal Model: | T-ALL xenograft[3] | | Dosage: | 15 mg/kg | | Administration: | Intraperitoneal injection (i.p.), twice weekly. | | Result: | Inhibited tumor growth and reduced the size of the spleen.
Showed massive infiltration and replacement of normal hematopoiesis by leukemia cells.
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| Animal Model: | NSG mice injected with DLL4-stimulated NOTCH1-mutated mino cells ex vivo[2] | | Dosage: | 20 mg/kg | | Administration: | Intraperitoneal injection (i.p.) | | Result: | Inhibited cleaved Notch1 but was not enough to cause a significant efficacy in tumor growth. |
| [References]
[1] Ferrarotto R, et al. A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors. Ann Oncol. 2018 Jul 1;29(7):1561-1568. DOI:10.1093/annonc/mdy171
[2] Silkenstedt E, et al. Notch1 signaling in NOTCH1-mutated mantle cell lymphoma depends on Delta-Like ligand 4 and is a potential target for specific antibody therapy. J Exp Clin Cancer Res. 2019 Nov 1;38(1):446. DOI:10.1186/s13046-019-1458-7
[3] Agnusdei V, et al. Therapeutic antibody targeting of Notch1 in T-acute lymphoblastic leukemia xenografts. Leukemia. 2014 Feb;28(2):278-88. DOI:10.1038/leu.2013.183 |
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