Abstract B132: Enhanced therapeutic effect of combined treatments with h7C10, a humanized antibody against insulin‐like growth factor‐1 receptor, and chemotherapeutic agents in xenograft models

IGF‐1 receptor (IGF‐1R) plays a key role in the development of numerous tumors. Blockade of IGF‐1R axis using monoclonal antibodies constitutes an interesting approach to inhibit tumor growth. We have previously described h7C10, a humanized anti‐IGF‐1R Mab, that exhibits a potent anti‐tumor activity both in vitro and in vivo . It blocks IGF‐1 and IGF‐2 induced signaling, inhibits cell proliferation and colony formation, induces cell cycle arrest and promotes IGF‐1R degradation. In this report, a panel of combinations of h7C10 with chemotherapeutic drugs were tested in vivo in xenograft models based on preliminary studies performed in vitro using the method described by Chou and Talalay. Our results confirmed a significant benefit of in vivo combinations of h7C10 with doxorubicin, docetaxel and paclitaxel. Data were less clear when h7C10 was combined to gemcitabine. An interesting combined effect was also noticed in mice treated by both h7C10 and 5‐FU. These findings demonstrate that h7C10 combined with established cancer therapeutics is highly effective in vivo against tumors expressing IGF‐1R and support clinical evaluation of h7C10 in combination with these drugs for the treatment of human cancers. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B132.