MM-141, an IGF-IR- and ErbB3-directed Bispecific Antibody, Overcomes Network Adaptations that Limit Activity of IGF-IR Inhibitors

Fitzgerald J, et al., 13(2):410-25, Mol Cancer Ther, 2014

The article describes the discovery and development of the first tetravalent bispecific antibody (named MM-141) which is capable of co-inhibiting two growth factor receptor families, namely IGF-IR and ErbB3. The MM-141 prevents PI3K/AKT/mTOR network adaptation by blocking the survival pathways and by degrading the receptor tyrosine kinase (RTK) complexes. Heregulin (HRG) is the ligand partner for ErbB3. HRG-ErbB3 autocrine loops are observed in ovarian cancer cells. Using an Octet system, authors were able to show that the antibody (MM-141) has the ability to block HRG binding to ErbB3. The HRG used for ligand blocking experiment was biotinylated and immobilized onto SA biosensors and the assays performed in the presence or in the absence of MM-141. Based on their detailed investigation, the authors suggest the potential of MM-141 to become an effective therapeutic agent for patients with solid tumors.

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