Approaches to optimize the use of monoclonal antibodies to epidermal growth factor receptor.
Preclinical and clinical studies consistently demonstrate the antitumor activity of the various monoclonal antibodies (mAbs) that block ligand binding to the extracellular domain of the epidermal growth factor receptor (EGFR). However, the objective antitumor activities of these agents are disproportionately lower than would be expected based on the high rates of expression, overexpression, and aberrations of EGFR in human malignancies, particularly carcinomas. Several technologic and clinical approaches are being explored to optimize the potency of these antibodies, such as humanization of the murine parent molecules, and conjugation and widening of the specificity of the mAb. Also, combined therapy with the different types of EGFR-interacting or other targeted agents may lead to a heightened potential. This review highlights the results of current approaches for improvement of the therapeutic indices of these agents.
Calvo
Emiliano
E
Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, 7979 Wurzbach Road, 4th Floor, Zeller Building, San Antonio, TX 78229, USA.
Rowinsky
Eric K
EK
D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D015195:Drug Design; D066246:ErbB Receptors / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors
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