IMC-A12 (ImClone Systems Incorporated), a fully human monoclonal IgG1 antibody that binds with high affinity to the IGF-IR, inhibits ligand-dependent receptor activation and downstream signaling. IMC-A12 also mediates robust internalization and degradation of the IGF-IR. In human tumor xenograft models, IGF-IR blockade by IMC-A12 results in rapid and profound growth inhibition of cancers of the breast, lung, colon, and pancreas, and many other neoplasms. Although promising single-agent activity has been observed, the most impressive effects of targeting the IGF-IR with IMC-A12 have been noted when this agent was combined with cytotoxic agents or other targeted therapeutics. So far, only a few preliminary human studies had been published, including in Ewing sarcoma. This drug may also have applications in autoimmunde disorders. It remains an experimental drug.
Eric K. Rowinsky et al, IMC-A12, a Human IgG1 Monoclonal Antibody to the Insulin-Like Growth Factor I Receptor Clin Cancer Res September 15, 2007 13; 5549s
Suman Malempati, Brenda Weigel, Ashish M. Ingle, Charlotte H. Ahern, Julie M. Carroll, Charles T. Roberts, Joel M. Reid, Stephen Schmechel, Stephan D. Voss, Steven Y. Cho, Helen X. Chen, Mark D. Krailo, Peter C. Adamson, and Susan M. Blane Phase I/II Trial and Pharmacokinetic Study of Cixutumumab in Pediatric Patients With Refractory Solid Tumors and Ewing Sarcoma: A Report From the Children’s Oncology Group JCO Jan 20, 2012:256-262
Terry J. Smith Insulin-Like Growth Factor-I Regulation of Immune Function: A Potential Therapeutic Target in Autoimmune Diseases? Pharmacological Reviews June 2010 vol. 62 no. 2 199-236
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