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.

摘要: 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 signaling often induces anti-tumor effect. The use specific antibodies, however, may limited by uptake organs that have high endogenous levels wild type such as liver. de2-7 (or EGFRvIII) a naturally occurring extracellular truncation found number including glioma, breast, lung prostate. Antibodies directed this variant provide alternative targeting strategy, although lower proportion tumors express restricts approach. We describe novel monoclonal (MAb 806) potentially overcomes difficulties associated with expressed on surface cells. MAb 806 bound transfected U87MG glioma cells (U87MG.Delta 2-7) affinity (approximately 1 x 10(9) M(-1)), but did not bind parental EGFR. Consistent observation, was unable soluble version containing domain. contrast, immobilization domain ELISA plates induced saturating dose response binding 806, suggesting can under certain conditions. also A431 cells, which due amplification gene large amounts Interestingly, only recognized 10% total molecules than determined specifically targeted U87MG.Delta 2-7 xenografts grown nude mice peak detected 8 h after injection. No observed. Following rapidly internalized macropinocytosis subsequently transported lysosomes, process probably contributes early observed xenografts. Thus, used or does when cell surface.