Targeting angiogenesis in multiple myeloma by the VEGF and HGF blocking DARPin^® protein MP0250: a preclinical study.

ABSTRACT: The investigational drug MP0250 is a multi-specific DARPin^® molecule that simultaneously binds and neutralizes VEGF and HGF with high specificity and affinity. Here we studied the antiangiogenic effects of the MP0250 in multiple myeloma (MM). In endothelial cells (EC) isolated from bone marrow (BM) of MM patients (MMEC) MP0250 reduces VEGFR2 and cMet phosphorylation and affects their downstream signaling cascades. MP0250 influences the secretory profile of MMEC and inhibits their in vitro angiogenic activities (spontaneous and chemotactic migration, adhesion, spreading and capillarogenesis). Compared to anti-VEGF or anti-HGF neutralizing mAbs, MP0250 strongly reduces capillary network formation and vessel-sprouting in a Matrigel angiogenesis assay. MP0250 potentiates the effect

SUBMITTER: Rao L 

PROVIDER: S-EPMC5862584 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature