Potency Of Bortezomib In Combination With Mp0250, A Bispecific Vegf- And Hgf-Targeting Darpin, In A Preclinical Multiple Myeloma Model.

e19574 Background: In multiple myeloma, tumor cells and stroma exert a reciprocal effect on each other that leads to tumor expansion in the bone marrow and bone destruction. Hepatocyte growth factor (HGF) is a main player in osteolytic bone destruction and also stimulates myeloma cell proliferation, migration and adhesion in the bone marrow. Additionally, VEGF plays a key neovascularization role in multiple myeloma. Therefore, we investigated whether MP0250, a bispecific DARPin simultaneously inhibiting tumor stroma HGF and VEGF, could potentiate the anti-tumor effect of the standard of care proteasome inhibitor bortezomib. Methods: MP0250 was tested as monotherapy and in combination with 0.6 mg/kg of bortezomib in an orthotopic murine model, where human multiple myeloma cells are implanted in the murine bone marrow. Tumor growth and invasion into the muscle were monitored by X-ray, whereas bone destruction was analyzed by microCT. Results: MP0250 significantly inhibited bone lysis and tumor invasion both...