EGF-PE24mutΔREDLK

EGF-PE24mutΔREDLK is an experimental recombinant targeted toxin designed for the treatment of cancers overexpressing the epidermal growth factor receptor (EGFR), such as advanced prostate cancer. It consists of a human epidermal growth factor (EGF) binding domain fused to a de-immunized 24 kDa variant of Pseudomonas Exotoxin A (PE24mut). A specific modification in this construct is the deletion of the C-terminal REDLK motif (a KDEL-like sequence), which normally facilitates retrograde transport from the Golgi to the endoplasmic reticulum. This deletion significantly reduces the toxin's baseline cytotoxicity by trapping it in endolysosomal compartments. However, when combined with endosomal escape enhancers like the plant-derived glycosylated triterpenoid SO1861, the toxin is released into the cytosol, where it inhibits protein synthesis by ADP-ribosylating elongation factor 2, leading to potent and selective synergistic cytotoxicity.