Matummab -: Solid tumor therapy humanized anti-EGFR monoclonal antibody

Membrane tyrosine kinase receptors in cancer cells are a particularly attractive therapeutic target. The epidermal growth factor (EGF) family of membrane receptors, and the epidermal growth factor receptor (EGFR) in particular, has emerged as one of the most promising targets. Ligand binding to the EGFR initiates multiple growth-regulatory signaling pathways, including the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways which regulate cellular gene transcription/proliferation and prosurvival signaling, respectively. One possible strategy to pharmacologically target EGFR is the use of anti-EGFR monoclonal antibodies (MAbs) to compete with activating EGFR ligands for binding to the extracellular domain. Matuzumab (EMD-72000) is a humanized IgG(1) MAb that not only binds with high specificity and affinity to EGFR, but also modulates antibody-dependent cellular cytotoxicity (ADCC). It has shown excellent antitumor activity against several human tumor types, including head and neck, lung, gastric and pancreatic cancers, and was chosen for further development. The efficacy, safety and pharmacokinetics of matuzumab as a single agent or in combination with other chemotherapeutics have been reported in several clinical trials. Matuzumab is presently undergoing phase II development for the treatment of solid tumors, including cervical, gastric, ovarian and non-small cell lung cancer (NSCLC).