Cixutumumab (IMC-A12) is a human monoclonal antibody for the treatment of solid tumors. This drug was developed by

ImClone Systems ImClone Systems Incorporated was a biopharmaceutical company dedicated to developing biologic medicines in the area of oncology. It was founded in 1984 and had its corporate headquarters in Bridgewater, New Jersey, and its research headquarters i ...

, since acquired by Eli Lilly, using

phage display Phage display is a laboratory technique for the study of protein–protein, protein–peptide, and protein– DNA interactions that uses bacteriophages (viruses that infect bacteria) to connect proteins with the genetic information that encodes ...

technology from Dyax. It is a fully human IgG1 monoclonal antibody directed against the human insulin-like growth factor-1 receptor (

IGF-1R The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 ( IGF-1) and by a related hormone called IGF-2. ...

) with potential antineoplastic activity. Cixutumumab selectively binds to membrane-bound IGF-1R, thereby preventing the binding of the ligand IGF-1 and subsequent activation of PI3K/AKT signaling pathway. Downregulation of the PI3K/AKT survival pathway may result in the induction of cancer cell apoptosis and may decrease cancer cellular proliferation. IGF-1R, a receptor tyrosine kinase of the insulin receptor superfamily overexpressed by many cancer cell types, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been implicated in tumorigenesis and metastasis.

Research

Phase II clinical trials have been completed in patients with non-small cell lung cancer, metastatic rhabdomyosarcoma, metastatic prostate cancer, metastatic pancreatic cancer, metastatic esophageal cancer, bone cancer, sarcoma, solid tumors, ocular melanoma, hepatocellular carcinoma, breast cancer and other forms of cancer. Despite these extensive trials, more than 45 phase I and II clinical trials in total, phase III trials have never been undertaken and Eli Lilly has removed cixutumumab from their development pipeline.

References

Monoclonal antibodies Experimental cancer drugs {{antineoplastic-drug-stub