Tagraxofusp (SL-401) is a potent IL-3 receptor inhibitor to inhibits plasmacytoid dendritic cells (pDCs) growth in multiple myeloma (MM) bone marrow (BM) microenvironment. Tagraxofusp has synergistic effect with Bortezomib (HY-10227) and Pomalidomide (HY-10984) to suppress multiple myeloma (MM)[1].
in vivo
Tagraxofusp (12-50 μg/kg; i.v.; 5 times per week for 3 weeks) blocks pDC-induced tumor growth and prolongs SCID-hu mice survival in subcutaneous INA-6 MM xenograft model[1].
Tagraxofusp (16 μg/kg; i.v.; 5 times per week for 1 weeks) enhances the anti-MM activity of 2.5 mg/kg Pomalidomide in CB-17 mice of subcutaneous MM xenograft model[1].
Animal Model:
SCID-hu mice with INA-6 MM cells[1]
Dosage:
12 μg/kg, 16 μg/kg, 25 μg/kg and 50 μg/kg
Administration:
Intravenous injection; for 5 consecutive days each week for 3 weeks
Result:
Blocked pDC-induced tumor growth and prolonged mice survival at 12 μg/kg.
Showed well tolerance at 16 μg/kg, while higher doses resulted in body weight decrease and toxicity.
Animal Model:
CB-17 mice with subcutaneous MM xenograft model[1]
Dosage:
16 μg/kg; with or without 2.5 mg/kg Pomalidomide (p.o.; 4 consecutive days weekly for 2 weeks)
Administration:
Intravenous injection; dose at 5 consecutive days for first week
Result:
Enhanced the anti-MM activity of proteasome inhibitor and immunomodulatory drug pomalidomide.
IC 50
IL-3
References
[1] Ray A, et al. A novel agent SL-401 induces anti-myeloma activity by targeting plasmacytoid dendritic cells, osteoclastogenesis and cancer stem-like cells. Leukemia. 2017 Dec;31(12):2652-2660. DOI:10.1038/leu.2017.135
