Treatment > Toxin Therapy

Meeting Abstract

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

A. E. Frankel, T. F. Liu, A. M. Thorburn, S. B. Tatter, M. C. Willingham

Wake Forest University School of Medicine, Winston-Salem, NC

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-EGFR antibody, and sensitivity to DAB₃₈₉EGF in tissue culture. 

Results. Tumor regressions and inhibition of growth were observed at all dose levels of DAB₃₈₉EGF as shown in the table below. 
At the highest dose levels (10 µg), histology showed only a few residual tumor cells. 
At the lower dose levels (1 and 5 µg), residual tumor was observed and retained EGFR positivity and DAB₃₈₉EGF sensitivity. 
The growth inhibition was significant for all dose levels analyzed by the Student's t test (one-sided) p=0.01, 0.005, and <0.0001 for DAB₃₈₉EGF 1µg, 5µg and 10µg, respectively. 

Conclusions. DAB₃₈₉EGF is an excellent candidate agent for interstitial therapy of high-grade gliomas.

Copyright 2004 American Society of Clinical Oncology All rights reserved worldwide.

Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-00895,00.asp