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TQM13-PE is an optimized recombinant fusion toxin consisting of a quadruply mutated interleukin-13 (TQM13) ligand fused to a potent derivative of Pseudomonas exotoxin (PE). The TQM13 component features four specific mutations (E13K, R66D, S69D, and K105R) designed to abrogate binding to the physiologically abundant IL13Rα1/IL4Rα receptor heterodimer while significantly increasing affinity for the tumor-restricted interleukin-13 receptor alpha 2 (IL13Rα2). This receptor is overexpressed in over 70% of glioblastoma multiformes (GBMs) and other malignancies such as melanoma, adenocarcinoma, ovarian cancer, and renal cell carcinoma. Upon binding to IL13Rα2, the fusion protein is internalized, and the Pseudomonas exotoxin payload induces cell death by inhibiting protein synthesis. Developed by researchers at Wake Forest University and the University of North Carolina, TQM13-PE has demonstrated therapeutic efficacy in orthotopic murine glioma models, showing specific killing of IL13Rα2-expressing tumor cells.
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