Abstract: The present application relates to compositions of modified toxins exhibiting cytotoxicity and/or reduced immunogenicity. Also provided are polypeptide toxophores from a modified diphtheria toxin, where modifications are in at least one amino acid residue of at least one T-cell epitope. Another aspect relates to a fusion protein which comprises a modified diphtheria toxin and a non-diphtheria toxin fragment that is a cell binding portion. Another aspect relates to the use of a modified diphtheria toxin for the treatment of a malignant disease or a non-malignant disease. A modified diphtheria toxin or fusion protein may be administered with one or more other agents.