摘要 |
Disclosed are site-specifically mutated cytotoxins which have an unpaired cysteine residue in or near the cytotoxin's receptor-binding site, and which retain essentially the same receptor-binding ability and cytotoxicity as the native cytotoxins provided they are not conjugated with a binding molecule. The cytotoxins suitable for use in the invention include pseudomonas exotoxin, and diphtheria toxin, and other proteinaceous plant or bacterial toxins which have one receptor-binding site per molecule. The cytotoxins are cross-linked through the free SH group of their unpaired cysteine residues to binding molecules (including monoclonal antibodies, fragments and other ligands) to form immunotoxins, and these immunotoxins do not bind to the cell surface receptors which are bound by the native cytotoxins. However, when the cross-linker is cleaved and the binding molecule is released, the cytotoxin regains its receptor-binding ability and its cytotoxicity. |