VivoGenie Anti-Human PDGFR (Olaratumab) Biosimilar (IVMB0486)

Platelet-derived growth factor receptor (PDGFR) is a class III receptor tyrosine kinase that upon binding to PDGF molecules, dimerizes and activates, triggering an intracellular signaling cascade essential to normal embryogenesis, development, migration, survival signaling, proliferation, cellular chemotaxis, and intracellular calcium metabolism¹. Hyperactive signaling along the PDGF/PDGFR axis drives pathogenesis in nonmalignant disorders (e.g., atherosclerosis, pulmonary fibrosis) and can promote tumor growth¹ or neurodegenerative disease². PDGFR is a target for anticancer therapeutic development¹. PDGF/PDGFR signaling influences cancer biology via autocrine growth stimulation of cancer cells, regulation of stromal-derived fibroblasts, and regulation of angiogenesis.

Olaratumab was developed as an anticancer therapeutic agent¹. Human IgG transgenic mice were immunized with PAE Rα cells and boosted with human PDGFRα extracellular domain (ECD)³. Splenocytes with high serum PDGFRα binding activity and high blocking titers against the PDGF/PDGFRα ligand receptor interaction were isolated, fused with myeloma cells, subcloned, and purified. Antibodies were further tested for binding to PDGFRα by direct binding ELISA and surface plasmon resonance, for blocking activity in solid-phase and cell-based ligand binding assays, and for receptor/ligand activation. Olaratumab was found to inhibit PDGF stimulated mitogenesis, PDGF-AA and PDGF-BB induced receptor phosphorylation, activation of the MAPK proliferation and Akt survival pathways, and in mouse xenograft models inhibits tumor growth and PDGFRα stimulation. Additionally, olaratumab inhibits cell proliferation and survival in mouse and human hepatoma cell lines 4 as well as PDGF-AA induced receptor phosphorylation and cell proliferation in ovarian cancer cells⁵. Clinical trials were initiated on the basis of these results^{6, 7, 8, 9}.

Olaratumab shows no cross reactivity with PDGFRβ in solid phase ELISA or cell-based phosphorylation assays, nor to mouse PDGFRα as determined by ELISA, mitogenic, and phosphorylation assays³.

Olaratumab clone AL10, a non-therapeutic biosimilar antibody for research use only was developed recombinantly and has the same variable regions as the original therapeutic.