Pseudomonas exotoxin a based toxins targeting epidermal growth factor receptor for the treatment of prostate cancer

Abstract: The epidermal growth factor receptor (EGFR) was found to be a valuable target on prostate cancer (PCa) cells. However, EGFR inhibitors mostly failed in clinical studies with patients suffering from PCa. We therefore tested the targeted toxins EGF-PE40 and EGF-PE24mut consisting of the natural ligand EGF as binding domain and PE40, the natural toxin domain of Pseudomonas Exotoxin A, or PE24mut, the de-immunized variant thereof, as toxin domains. Both targeted toxins were expressed in the periplasm of E.coli and evoked an inhibition of protein biosynthesis in EGFR-expressing PCa cells. Concentration- and time-dependent killing of PCa cells was found with IC50 values after 48 and 72 h in the low nanomolar or picomolar range based on the induction of apoptosis. EGF-PE24mut was found to be about 11- to 120-fold less toxic than EGF-PE40. Both targeted toxins were more than 600 to 140,000-fold more cytotoxic than the EGFR inhibitor erlotinib. Due to their high and specific cytotoxicity, the EGF-based targeted toxins EGF-PE40 and EGF-PE24mut represent promising candidates for the future treatment of PCa

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Toxins. - 12, 12 (2020) , 753, ISSN: 2072-6651

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2020
• Creator: Fischer, Alexandra ; Wolf, Isis ; Fuchs, Hendrik Ansgar ; Masilamani, Anie P. ; Wolf, Philipp

Further information

• DOI: 10.3390/toxins12120753
• URN: urn:nbn:de:bsz:25-freidok-1700867
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:34 AM CEST