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The insulin-like growth factor-1 receptor (IGF-1R) is a critical component in the cell signaling pathways important for cell growth and proliferation. IGF-1R is highly expressed in breast, lung and colorectal cancers, while high IGF-1 plasma levels have been associated with increased risk for prostate, breast, colon and lung cancers. Targeting the IGF-1R pathway presents a good opportunity for therapeutic intervention against cancer growth. We have recently developed a fully human monoclonal antibody SCH 717454 (19D12) that binds to the human IGF-1R with high affinity (1.65 X10-10 M), neutralizes IGF-1 binding and inhibits IGF-1R auto-phosphorylation. We have previously demonstrated the efficacy of SCH 717454 in a variety of human cancer xenograft models of breast, colorectal, lung, ovarian and pediatric cancers. Here, we report significant improvement of in vivo efficacy by combining SCH 717454 with chemo as well as targeted therapeutic agents in several human cancer xenograft models of neuroblastoma and breast cancers. Immuno-histological studies of xenograft tumor samples will also be presented.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA