Novel monoclonal antibody specific for the de2-7 epidermal growth factor receptor (EGFR) that also recognizes the EGFR expressed in cells containing amplification of the EGFR gene

Terrance Grant Johns, Elisabeth Stockert, Gerd Ritter, Achim A Jungbluth, H J Su Huang, Webster K Cavenee, Fiona E Smyth, Cathrine M Hall, Nadine Watson, Edouard C Nice, William J Gullick, Lloyd J Old, Antony W Burgess, Andrew M Scott

Research output: Contribution to journalArticleResearchpeer-review

117 Citations (Scopus)

Abstract

In some respects, the EGFR appears to be an attractive target for tumor-targeted antibody therapy: it is overexpressed in many types of epithelial tumor and inhibition of signaling often induces an anti-tumor effect. The use of EGFR specific antibodies, however, may be limited by uptake in organs that have high endogenous levels of the wild type EGFR such as the liver. The de2-7 EGFR (or EGFRvIII) is a naturally occurring extracellular truncation of the EGFR found in a number of tumor types including glioma, breast, lung and prostate. Antibodies directed to this tumor specific variant of the EGFR provide an alternative targeting strategy, although the lower proportion of tumors that express the de2-7 EGFR restricts this approach. We describe a novel monoclonal antibody (MAb 806) that potentially overcomes the difficulties associated with targeting the EGFR expressed on the surface of tumor cells. MAb 806 bound to de2-7 EGFR transfected U87MG glioma cells (U87MG.Delta 2-7) with high affinity (approximately 1 x 10(9) M(-1)), but did not bind parental cells that express the wild type EGFR. Consistent with this observation, MAb 806 was unable to bind a soluble version of the wild type EGFR containing the extracellular domain. In contrast, immobilization of this extracellular domain to ELISA plates induced saturating and dose response binding of MAb 806, suggesting that MAb 806 can bind the wild type EGFR under certain conditions.
Original languageEnglish
Pages (from-to)398 - 408
Number of pages11
JournalInternational Journal of Cancer
Volume98
Issue number3
Publication statusPublished - 2002
Externally publishedYes

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