CYTOTOXICITY OF TGF-ALPHA-PE40 AND CORRELATION TO EXPRESSION OF EPIDERMAL GROWTH-FACTOR RECEPTOR

TGF alpha-PE40 is a chimeric protein composed of transforming growth f actor alpha (TGF alpha) linked to a modified Pseudomonas exotoxin (PE4 0). We tested the in vitro cytotoxicity of TGF alpha-PE40 on 23 differ ent solid human tumour xenografts established in nude mice and human b one marrow cells from healthy donors, utilising a modified clonogenic assay. In order to distinguish non-specific toxicity from the targeted effects of TGF alpha-PE40, epidermal growth factor receptor (EGFR) ex pression of the tumours studied was assessed by Northern blot, slot bl ot and immunohistochemistry. TGF alpha-PE40 demonstrated differential cytotoxicity on human tumour xenografts in the clonogenic assay. No to xicity on human bone marrow cells was observed. In vitro activity of T GF alpha-PE40 showed a significant correlation with the expression of EGF receptors as determined by immunohistochemistry and slot blot. Fur ther studies will be performed in order to determine the in vivo activ ity of this compound in tumour-bearing nude mice.