An antibody directed against PDGF receptor β enhances the antitumor and the anti-angiogenic activities of an anti-VEGF receptor 2 antibody

Platelet-derived growth factor (PDGF) and its receptors (PDGFR) play important roles in tumorigenesis through stimulating tumor growth and promoting angiogenesis via enhancing pericyte recruitment and vessel maturation. Here we produced a neutralizing antibody, 1B3, directed against mouse PDGFRβ. 1B3 binds to PDGFRβ with high affinity (9 × 10−11 M) and blocks PDGF-BB from binding to the receptor with an IC50 of ∼1.2 nM. The antibody also blocks ligand-stimulated activation of PDGFRβ and downstream signaling molecules, including Akt and MAPK p42/44, in tumor cells. In animal studies, 1B3 significantly enhanced the antitumor and the anti-angiogenic activities of DC101, an antibody directed against mouse vascular endothelial growth factor receptor 2, in a pancreatic (BxPC-3) and a non-small cell lung (NCI-H460) tumor xenograft models. Treatment with the combination of 1B3 and DC101 in BxPC-3 xenograft-bearing mice resulted in tumor regression in 58% of mice compared to that in 18% of mice treated with DC101 alone. Taken together, these results lend great support to use PDGFRβ antagonists in combinations with other antitumor and/or anti-angiogenic agents in the treatment of a variety of cancers.