Reports on over-expression of the epidermal growth factor receptor (EGFR) in bladder cancer and its function in tumorigenesis have suggested to target this antigen.
We generated the targeted toxin EGF-PE40 consisting of the human epidermal growth factor (EGF) as the binding domain and PE40, a truncated version of Pseudomonas Exotoxin A, as the toxin domain. EGF-PE40 was tested on EGFR-expressing bladder cancer cells in view of binding via flow cytometry, and cytotoxicity via WST viability assay. Induction of apoptosis was examined by western blot.
The targeted toxin specifically triggered cytotoxicity in the bladder cancer cells with 50% inhibitory concentration (IC50) values in the low nanomolar or picomolar range, and was about 1,250- to 1,500-fold more cytotoxic than the EGFR inhibitor erlotinib. Cytotoxicity of EGF-PE40 was based on the induction of apoptosis.
EGF-PE40 represents a promising candidate for the future treatment of bladder cancer.
Anticancer research. 2021 Aug [Epub]
Anie Priscilla Masilamani, Alexandra Fischer, Susanne Schultze-Seemann, Irina Kuckuck, Isis Wolf, Franz Friedrich Dressler, Christian Gratzke, Philipp Wolf
Faculty of Medicine, University of Freiburg, Freiburg, Germany., Insitute of Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany., Faculty of Medicine, University of Freiburg, Freiburg, Germany .