Ipafricept (OMP-54F28; FZD8-Fc) is a first class recombinant fusion protein with the extracellular part of the human frizzled-8 receptor fused to a human IgG1 Fc fragment that binds Wnt ligands, which blocks Wnt signaling. Ipafricept reduces tumor growth and results in a decrease in both liver and lung metastases combined with Gemcitabine in pancreatic cancer mouse models. Ipafricept shows solid tumor inhibition activity with well tolerance, such as desmoid tumor, germ cell cancer, ovarian cancer.
Ipafricept (10 μg/mL, 4 h) inhibits the pro-proliferative and and migration effects of peptide RL-QN15 on human embryonic stem cells (hESCs) [3].Ipafricept (10 μg/mL, 0-48 h) reverses the RL-QN15-induced activation of the Wnt/β-catenin signaling pathway, leading to the reversal of the effects of RL-QN15 on the proliferation, migration and stemness of hESCs[3].
Ipafricept (10 mg/kg weekly or 25 mg/kg every 2 weeks, i.p., for 42 days) promotes tumor growth inhibition when combined with weekly Gemcitabine (50 mg/kg or 5 mg/kg weekly) and Nab-paclitaxel (10 mg/kg weekly) in pancreatic cancer xenograft mouse models[2].Ipafricept (45 mg/kg every 2 weeks, i.p., for 42 days) results in greater antitumor activity of WNT blockade and tumor growth inhibition in combination with Nab-paclitaxel (7.5 mg/kg every week) than Carboplatin (30 mg/kg every week) in ovarian cancer xenograft mouse models[2].Ipafricept (10 mg/kg, s.c., administered on day 0 and 3) competes with RL-QN15 for binding, reducing the interaction of RL-QN15 with FZD8, thereby counteracting its activation of the Wnt/β-catenin signaling pathway in mouse full-thickness skin injury models[3].
References:
[1]. Jimeno A, et al. A First-in-Human Phase I Study of the Anticancer Stem Cell Agent Ipafricept (OMP-54F28), a Decoy Receptor for Wnt Ligands, in Patients with Advanced Solid Tumors. Clin Cancer Res. 2017 Dec 15;23(24):7490-7497.
[2]. Fischer MM, et al. WNT antagonists exhibit unique combinatorial antitumor activity with taxanes by potentiating mitotic cell death. Sci Adv. 2017 Jun 21;3(6):e1700090.
[3]. Li Y, et al. Peptide RL-QN15 regulates epidermal stem cell function to accelerate wound healing via the FZD8/β-catenin axis[J]. Authorea Preprints, 2024.