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The insulin-like growth factors (IGFs) signaling system has been shown to play important roles in neoplasia.The IGF receptor type 1 (IGF-IR) is overexpressed in many types of solid and hematopoietic malignancies,and there is substantial experimental and clinical evidence that targeting IGF-IR is a promising therapeutic strategy against cancer.It has been previously reported that a mouse monoclonal antibody (mAb),4G 11,blocked IGF-Ⅰ binding to IGF-IR and downregulated the IGF-IR in MCF-7 cells.We cloned this antibody,constructed a human-mouse chimeric antibody,designated m590,and characterized it.The chimeric IgG1 m590 bound to cell-associated IGF-IR on NWT c43 stably transfected cells and MCF-7 breast cancer cells as efficiently as the parental murine antibody.Using purified IGF-IR extracellular domains,we found that both the chimeric m590 and the parental 4G11 antibodies bind to conformational epitopes on IGF-IR.Neither of these antibodies bound to the insulin receptor (IR) ectodomain.Furthermore,IgG1 m590 blocked the binding of IGF-Ⅰ and IGF-Ⅱ to IGF-IR and inhibited both IGF-Ⅰ and IGF-Ⅱ induced phosphorylation of IGF-IR in MCF-7 cells.These results suggest that m590 could be an useful antibody in diagnosis and treatment of cancer as well as a research tool.