Tagraxofusp

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].

Research Areas >> Cancer

Signaling Pathways >> Immunology/Inflammation >> Interleukin Related

IL-3

Tagraxofusp (0-1367 pM; 72 h) inhibits pDCs viability, as well as pDC-induced proliferation of MM cells.Tagraxofusp (0-136.7 pM; 2-3 weeks) inhibits osteoclast formation and bone resorption, as well as stabilizes osteoblast formation[1]. Tagraxofusp (0-13.67 nM; 48 h) targets tumor-initiating stem-like cells in MM[1]. Cell Viability Assay[1] Cell Line: Cancer stem-like cells in MM Concentration: 0 nM, 0.013 nM, 0.13 nM, 1.3 nM, 13.67 nM Incubation Time: 48 hours Result: Inhibits cancer stem-like cells with s of 30 pM (pDCs), 50 nM (MM-SP-Oct4 cells), 75 pM (RPMI-8226-Oct4 cells), 350 pM (MM-SP cells), and 1367 pM (RPMI-8226 cells), respectively.

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.

[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.