Targeted delivery of an ADP-ribosylating bacterial toxin into cancer cells

Abstract: The actin cytoskeleton, a central component of many cellular functions, is an attractive target for bacterial toxins. The ADP-ribosyltransferase TccC3 of the insect pathogen Photorhabdus luminescence modifies actin to force its aggregation. We intended to transport the catalytic part of this toxin preferentially into cancer cells. For this we used a toxin transporter which was redirected to the Epidermal Growth Factor Receptor (EGFR) or to the human EGF receptor 2 (HER2), which are overexpressed in several cancer cells. Protective antigen (PA) of anthrax toxin forms a pore through which the two catalytic parts of anthrax toxin (lethal factor and edema factor) or other proteins can be transported into mammalian cells. Here, we used PA as a double mutant (N682A, D683A) which cannot bind to the two natural anthrax receptors and instead bind to EGFR or to HER2. We developed a cellular model system composed of two cell lines representing HER2 overexpressing esophageal adenocarcinomas (EACs) and EGFR overexpressing esophageal squamous cell carcinomas (ESCCs). We studied specificity and efficiency of the re-directed anthrax pore for transport of TccC3 toxin. Moreover, we established Photorhabdus luminescence TccC3 as a suitable transported catalytic part for the development of a targeted toxin selectively killing cancer cells

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Scientific Reports. 7 (2017), 41252, DOI 10.1038/srep41252, issn: 2045-2322 ; IN COPYRIGHT http://rightsstatements.org/page/InC/1.0 rs

Classification and Topics

• Keyword: Immunotoxin ; Krebs ; Onkologie

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2017
• Creator: Zahaf, Nour-Imene ; Lang, Alexander E. ; Kaiser, Lars ; Fichter, Christiane Daniela ; Laßmann, Silke ; Augspach, Anke ; Aktories, Klaus ; Schmidt, Gudula
• Contributor: Albert-Ludwigs-Universität Freiburg. Institut für Experimentelle und Klinische Pharmakologie und Toxikologie ; Institut für Klinische Pathologie. Freiburg im Breisgau ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät ; Tumorzentrum Freiburg - CCCF ; Albert-Ludwigs-Universität Freiburg. Centre for Biological Signalling Studies ; DKTK German Cancer Consortium ; Albert-Ludwigs-Universität Freiburg

Further information

• DOI: 10.1038/srep41252
• URN: urn:nbn:de:bsz:25-freidok-126992
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:57 PM CET