Mitotoxins: growth factor-targeted cytotoxic molecules

Abstract

When the selective specificity and exquisite affinity of growth factors for their receptors is conferred to protein toxins, the chimeric molecules so generated become potent cytotoxins. Chimera are produced by the chemical conjugation of the two proteins or by expression of fusion proteins in bacterial expression systems. The toxic moiety, usually a ribosome-inactivating protein or a fragment of a bacterial toxin, is internalized into target cells by receptor-mediated endocytosis. Release of the receptor's ligand in the endosome allows the toxic moiety to exert its action on protein synthesis. Accordingly, the potent catalytic activity of the toxin results in a sensitivity of some cells to picomolar quantities of the mitotoxin. This review discusses the numerous growth factor-toxins that have been created and describes some of their applications.