Tovetumab

Tovetumab (MEDI-575) is an anti-PDGFRα monoclonal antibody that selectively blocks the PDGFRα signal transduction. Tovetumab can be used in the research of glioblastoma and non-small cell lung cancer (NSCLC)[1][2].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PDGFR

PDGFRα

Tovetumab (10-100 nM, 1-2 h) binds to PDGFRα on H1703 cells (determined by Alexa647-labeled tovetumab)[1]. Tovetumab (0.001-10 nM, 10 min) inhibits ligand-induced phosphorylation of human PDGFRα in MG-63 cells[2]. Tovetumab (0.001-100 nM, 72 h ) inhibits Ligand-induced proliferation of cancer-associated fibroblasts (CAFs) [2].

Tovetumab (0.6-60 mg/kg, i.v.) blocks the PDGFRα-mediated elimination of PDGF-AA, leading to an increase in circulating PDGF-AA level in Cynomolgus monkeys[1]. Tovetumab (10 mg/kg, i.p., twice a week) inhibits tumor growth in U118 glioma xenografts[2]. Animal Model: Cynomolgus monkey[1] Dosage: 0.6, 6.0, and 60 mg/kg Administration: Intravenous injection (i.v.) Result: Induced > 100- fold increases in circulating concentrations of PDGF-AA. Animal Model: U118 glioma xenografts (CB17 SCID)[2] Dosage: 10 mg/kg Administration: Intraperitoneal injection (i.p.), twice per week. Result: Produced 101% inhibition of tumor growth.

[1]. Meina Liang, et al. A Novel Pharmacodynamic Biomarker and Mechanistic Modeling Facilitate the Development of Tovetumab, a Monoclonal Antibody Directed Against Platelet-Derived Growth Factor Receptor Alpha, for Cancer Therapy. AAPS J. 2020 Nov 18;23(1):4.

[2]. Naomi Laing, et al. Inhibition of platelet-derived growth factor receptor α by MEDI-575 reduces tumor growth and stromal fibroblast content in a model of non-small cell lung cancer. Mol Pharmacol. 2013 Jun;83(6):1247-56.