DT388IL3[D125-133]

DT388IL3[D125-133] is a recombinant fusion toxin designed to target the interleukin-3 receptor (IL-3R) on leukemic cells, particularly in acute myeloid leukemia (AML). It consists of a truncated form of diphtheria toxin (DT388), which lacks the native cell-binding domain but retains the catalytic and translocation domains, fused to a modified human interleukin-3 (IL-3) ligand. The modification in this specific variant is an eight amino acid deletion from the C-terminus of the IL-3 molecule (residues 125-133), which is engineered to enhance the binding affinity of the fusion protein to the IL-3 receptor. Upon binding to IL-3R, the molecule is internalized via receptor-mediated endocytosis. The diphtheria toxin moiety then translocates into the cytosol, where it catalyzes the ADP-ribosylation of elongation factor 2 (EF-2), thereby inhibiting protein synthesis and inducing apoptosis. Preclinical ex vivo studies have shown that this variant possesses significantly higher cytotoxic activity against AML colony-forming cells compared to the unmodified native DT388IL3 fusion protein, while maintaining a favorable toxicity profile against normal hematopoietic progenitors.

Other names

DT388IL3 variantDT-388IL3 variantDT 388IL3 variantDT388-IL3 deletion mutantDT-388-IL3 deletion mutantDT 388-IL3 deletion mutant