Anti-EGF receptor monoclonal antibodies: biological studies and potential clinical applications.
We have produced two monoclonal antibodies (mAbs), 528 IgG2a and 225 IgG1, which bind to the human EGF receptor with an affinity comparable to EGF, compete with EGF for binding to the receptor, and prevent EGF-induced activation of receptor tyrosine kinase. The mAbs inhibit the proliferation of a number of human tumor cells bearing high numbers of EGF receptors in culture and in nude mouse xenographs. A431 xenographs bearing high numbers of EGF receptors can be imaged with 111In-labeled mAb. Phase I trials were initiated in patients with advanced squamous cell carcinoma of the lung, which consistently expresses high numbers of EGF receptors. 111In-labeled 225 IgG1 was given by single intravenous infusion. Preliminary results show no toxicity from doses up to 120 mg. Tumor visualization was seen to be dose-related. However, as with other imaging studies with indium-labeled antibodies, significant liver and bowel isotope uptake was observed. Further dose escalation is ongoing to assess the relationship between dose and tumor uptake.
Mendelsohn
J
J
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002455:Cell Division; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors