In vivo pre-clinical evaluation of the IGF-1R-specific antibody AVE1642 as single agent and in combination with Velcade ® /Bortezomib

4115 The insulin-like growth factor 1 receptor (IGF-1R) has been strongly implicated in the pathogenesis and progression of various cancers, providing a rationale for therapeutically targeting IGF-1R. To this end, we have developed a monoclonal antibody (mAb), EM164 and its humanized version AVE1642, which effectively inhibits growth of primary and secondary tumors (Poster abstract AACR 2006). Here we characterize further the therapeutic activity of AVE1642 as a single agent and evaluate the in vivo activity of AVE1642 in combination with bortezomib (Velcade ® ). Breast cancer frequently metastasises to the bone and to the lung. To evaluate the effect of AVE1642 on human breast cancer cells in the bone milieu, we implanted in the tibia of SCID mice, MDA-MB-231-Luc-D3H1 cells expressing the firefly luciferase gene. In recipient mice treated bi-weekly for 8 weeks with AVE1642 at 40 mg/kg/injection (day 1 - 80 post implantation), tumor growth measured by bioluminescent signal before onset of osteolysis, was significantly (p In conclusion, AVE1642 effectively inhibited tumor growth within the bone and pulmonary microenvironment. The combination of AVE1642 with bortezomib, was found more active than the individual agents, showing the clinical potential of this antibody in patients with multiple myeloma.