Diphtheria toxin variant

摘要

The present invention relates to methods and compositions of modified variants of diphtheria toxin (DT) that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome. One aspect of the present invention relates to a polypeptide toxophore from a modified DT, wherein the mutation is the substitution or deletion at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of native DT. Another aspect of the present invention relates to a fusion protein which comprises a modified DT and a non-DT fragment. Another aspect of the present invention relates to the use of modified DT for the treatment of cancer.

主权项

1. An isolated polypeptide comprising amino acid residues 1-380 of SEQ ID NO:4, wherein the polypeptide comprises amino acid substitution at position I290 or D291 of SEQ ID NO:4, and, optionally with at least one amino acid substitution or deletion made within the regions selected from the group consisting of residues 7-9, 29-31 and 290-292, and wherein said DT variant has cytotoxicity comparable to that of a DT molecule having a sequence of SEQ ID NO:4.