Recombinant toxin DAB389EGF produces regressions of human glioma xenografts in nude mice

Abstract

3101 Background: DAB389EGF, composed of the catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor is selectively toxic to epidermal growth factor receptor (EGFR) overexpressing human glioma cells (Curr Pharm Biotech, 4, 39, 2003; Cancer Res, 63, 1834, 2003; J Neurooncol, 65, 77, 2003; Bioconj Chem, 14, 1167, 2003). Based on this in vitro activity and the high frequency of EGFR expression in human gliomas (Mol Cancer Ther, 2, 783, 2003), we examined the in vivo anti-glioma activity of DAB389EGF. Methods: Groups of five 8 wk old female athymic nu/nu mice were inoculated with 10 million U87MG human glioma cells subcutaneously. After tumors grew to at least 100 mm3, intra-tumor injections were given in 50 microliter volume every other day of saline or DAB389EGF (1, 5, or 10 μg). Tumor size and animal weights were recorded. After one month, animals were euthanized, and tumor samples were examined by routine histology, immuno-reactivity with anti-EGF...