Cytotoxic properties of DAB sub(486)EGF and DAB sub(389)EGF, epidermal growth factor (EGF) receptor-targeted fusion toxins

Elevated expression of the receptor for epidermal growth factor (EGF) is a characteristic of several malignancies including those of the breast, bladder, prostate, lung, and neuroglia. To therapeutically target the cytotoxic action of diphtheria toxin to EGF receptor-expressing tumor cells, we have...

Full description

Saved in:
Bibliographic Details
Published inThe Journal of biological chemistry Vol. 266; no. 31; pp. 21118 - 21124
Main Authors Shaw, J P, Akiyoshi, DE, Arrigo, DA, Rhoad, A E, Sullivan, B, Thomas, J, Genbauffe, F S, Bacha, P, Nichols, J C
Format Journal Article
LanguageEnglish
Published 01.01.1991
Subjects
corynebacterium diphtheriae
Online AccessGet full text

Cover

More Information
Summary:Elevated expression of the receptor for epidermal growth factor (EGF) is a characteristic of several malignancies including those of the breast, bladder, prostate, lung, and neuroglia. To therapeutically target the cytotoxic action of diphtheria toxin to EGF receptor-expressing tumor cells, we have constructed a hybrid gene in which the sequences for the binding domain of diphtheria toxin have been replaced by those for human EGF. The resulting fusion toxins, DAB sub(486)EGF and DAB sub(389)EGF, bind specifically to the EGF receptor and inhibit protein synthesis in a variety of EGF receptor expressing human tumor cell lines with an IC sub(50) as low as 0.1 pM. Comparisons of DAB sub(486)EGF and DAB sub(389)EFG showed that DAB sub(389)EGF was consistently 10- to 100-fold more cytotoxic than DAB sub(486)EGF.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
content type line 23
ObjectType-Feature-1
ISSN:0021-9258