Diphtheria toxin-based targeted toxins that target glioblastoma multiforme

Targeted toxins (TTs) are compounds that bind cell surface receptors overexpressed on cancer cells. After the molecule enters the cell, the toxin component migrates to the ribosomes where it blocks protein synthesis killing the cell. Most of these proteins are recombinant and contain a carrier ligand or antibody attached to a modified bacterial toxin such as diphtheria toxin (DT). With respect to cancer, these fusion proteins are active against brain tumor cells that are resistant to chemotherapy and radiation therapy. The toxicity profile for TTs is acceptable and they have been safe in animal studies and demonstrated a therapeutic response in early clinical trials. Those barriers to the successful treatment of brain tumors include poor tumor penetration, immune recognition of DT and the heterogeneity of cancer.