Anti-Human PDGF-R alpha Therapeutic Antibody (Olaratumab)

Figure 1 Olaratumab prevents ligand-induced phosphorylation of PDGFRa.

A–C, A-204 and HuO9 cells (A), which only express PDGFRa, G-402 and MG-63 cells (B), which express both PDGF receptors, or G-401 cells (C), which are PDGFRb positive, were treated with 1 mmol/L IgG or olaratumab for 15 minutes and then stimulated with individual PDGFs (5 nmol/L). Whole-cell lysates were probed for phosphorylation of PDGF receptors and downstream effectors AKT and ERK1/2.

Lowery, C. D., Blosser, W., Dowless, M., Knoche, S., Stephens, J., Li, H., ... & Guo, Q. (2018). Olaratumab exerts antitumor activity in preclinical models of pediatric bone and soft tissue tumors through inhibition of platelet-derived growth factor receptor α. Clinical Cancer Research, 24(4), 847-857.

Figure 2 Olaratumab reduces osteosarcoma and MRT cell invasion in vitro.

A–E, A-204 (A), HuO9 (B), G-402 (C), MG-63 (D), or G-401 cells (E) were evaluated for cell invasion using a simplified Boyden chamber assay. Cells were incubated with IgG or olaratumab; individual PDGFs (5 nmol/L each, with the exception of 25 nmol/L PDGF-DD) or FBS served as chemoattractants. After 48 hours, the number of invasive cells was quantified using a fluorescence-based method and normalized to the serum-free media (SFM) IgG control. Results are presented as the summary of duplicate (G-402) or triplicate experiments SEM. P values were calculated using the Student t test. Significance indicators: , P < 0.05, P < 0.001.

Lowery, C. D., Blosser, W., Dowless, M., Knoche, S., Stephens, J., Li, H., ... & Guo, Q. (2018). Olaratumab exerts antitumor activity in preclinical models of pediatric bone and soft tissue tumors through inhibition of platelet-derived growth factor receptor α. Clinical Cancer Research, 24(4), 847-857.

Figure 3 Olaratumab inhibits tumor growth in A-204 and HuO9 cell line–derived xenograft mouse models.

A and B, Mice with A-204 subcutaneous xenografts were treated with either 40 mg/kg IgG control or 40 mg/kg olaratumab three times weekly for 4 weeks. A, Average tumor volume SEM (n ¼ 11/group) during the treatment period is shown. B, Waterfall plot of %Dtumor/control or %regression for individual animals at day 30. One animal in the treatment arm was found dead on day 17 and was not included in downstream analysis. C and D, Mice bearing HuO9 subcutaneous xenografts were treated with olaratumab (60 mg/kg)/1E10 (20 mg/kg) twice weekly and/or cisplatin or doxorubicin (5 mg/kg) once weekly. Treatment began at day 44 (dotted line) and continued for 5 weeks. C, A single HuO9 in vivo experiment is displayed in two separate graphs with the same control and olaratumab/1E10 arms but different chemotherapy-containing arms containing chemotherapy (left, cisplatin; right, doxorubicin). The graph displays average tumor volume SEM (n ¼ 6/group). D, Waterfall plot of individual %Dtumor/control or %regression at day 60. P values for tumor growth curves are displayed in Supplementary Table S4. PD, progressive disease (>10% growth); SD, stable disease ( 50%–10% growth); PR, partial regression ( 50% and>14 mm3).

Lowery, C. D., Blosser, W., Dowless, M., Knoche, S., Stephens, J., Li, H., ... & Guo, Q. (2018). Olaratumab exerts antitumor activity in preclinical models of pediatric bone and soft tissue tumors through inhibition of platelet-derived growth factor receptor α. Clinical Cancer Research, 24(4), 847-857.