Antitumor activity of combinations of antibodies directed against different epitopes on the extracellular domain of the human EGF receptor

作者: H. Modjtahedi , S. A. Eccles , G. Box , J. Styles , C. J. Dean

DOI: 10.1007/BF03033871

关键词: EpitopeCancer researchTransforming growth factorImmunologyBiologyAntibodyReceptorEpidermal growth factorIn vitroEpidermal growth factor receptorMonoclonal antibodyBiophysicsCell biology

摘要: The receptor (EGFR) for epidermal growth factor (EGF) and transforming alpha (TGFα) is often overexpressed in certain types of human malignancy high levels expression the and/ or coexpression factors. EGF TGFα have also been correlated with poor prognosis many patients. We produced a number rat monoclonal antibodies (MAbs) against four distinct epitopes on external domain are currently evaluating their potential therapeutic use. Nine these MAbs were found to inhibit binding TGF tumor cells able vitro vivo that overexpress receptor. Here, we describe results experiments determine antitumor activity combination treatment two directed separate EGFR. Our showed xenografts anti-EGFR bind was not as effective ICR62 alone, which binds epitope C EGFR IgG2b isotype. A phase I clinical trial antibody underway Royal Marseden Hospital (UK) patients head neck lung carcinomas.

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