Anti-Human PDGFR (Olaratumab) – Fc Muted™

Human PDGFRA

This biosimilar antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration.

Liquid

Recombinant biosimilar antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates.

To protect mouse colonies from infection by pathogens and to assure that experimental preclinical data is not affected by such pathogens, all of Leinco’s recombinant biosimilar antibodies are tested and guaranteed to be negative for all pathogens in the IDEXX IMPACT I Mouse Profile.

Functional grade preclinical antibodies may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at ≤ -70°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only (RUO). Non-Therapeutic.

2-8°C Wet Ice

Olaratumab activity is directed against human PDGFRα. This non-therapeutic biosimilar antibody uses the same variable region sequence as the therapeutic antibody Olaratumab. This product is for research use only.

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.

PDGFRα is expressed on platelets, megakaryocytes, fibroblasts, pericytes, vascular smooth muscle cells, neurons, and myoblasts. Malignant cells from several types of cancer (ovary, prostate, breast, lung, brain, skin, bone, gastrointestinal, kidney) can also express PDGFRα.

PDGFRA, CD140b