Pseudomonas exotoxin A: from virulence factor to anti-cancer agent
- PMID: 18948059
- DOI: 10.1016/j.ijmm.2008.08.003
Pseudomonas exotoxin A: from virulence factor to anti-cancer agent
Abstract
The pathogenic bacterium Pseudomonas aeruginosa has the ability to cause severe acute and chronic infections in humans. Pseudomonas exotoxin A (PE) is the most toxic virulence factor of this bacterium. It has ADP-ribosylation activity and decisively affects the protein synthesis of the host cells. The cytotoxic pathways of PE have been elucidated, and it could be shown that PE uses several molecular strategies developed under evolutionary pressure for effective killing. Interestingly, a medical benefit from this molecule has also been ascertained in recent years and several PE-based immunotoxins have been constructed and tested in preclinical and clinical trials against different cancers. In these molecules, the enzymatic active domain of PE is specifically targeted to tumor-related antigens. This review describes the current knowledge about the cytotoxic pathways of PE. Additionally, it summarizes preclinical and clinical trials of PE-based immunotoxins and furthermore discusses current problems and answers with these agents.
Similar articles
-
Designing the furin-cleavable linker in recombinant immunotoxins based on Pseudomonas exotoxin A.Bioconjug Chem. 2015 Jun 17;26(6):1120-8. doi: 10.1021/acs.bioconjchem.5b00190. Epub 2015 Jun 3. Bioconjug Chem. 2015. PMID: 25997032 Free PMC article.
-
Mechanisms of Resistance to Immunotoxins Containing Pseudomonas Exotoxin A in Cancer Therapy.Biomolecules. 2020 Jun 30;10(7):979. doi: 10.3390/biom10070979. Biomolecules. 2020. PMID: 32630017 Free PMC article. Review.
-
A guide to taming a toxin--recombinant immunotoxins constructed from Pseudomonas exotoxin A for the treatment of cancer.FEBS J. 2011 Dec;278(23):4683-700. doi: 10.1111/j.1742-4658.2011.08182.x. Epub 2011 Jun 2. FEBS J. 2011. PMID: 21585657 Free PMC article. Review.
-
Pseudomonas exotoxin and recombinant immunotoxins derived from it.Ann N Y Acad Sci. 1993 Jun 23;685:740-5. doi: 10.1111/j.1749-6632.1993.tb35935.x. Ann N Y Acad Sci. 1993. PMID: 8363279 Review.
-
Protection of the Furin Cleavage Site in Low-Toxicity Immunotoxins Based on Pseudomonas Exotoxin A.Toxins (Basel). 2016 Jul 25;8(8):217. doi: 10.3390/toxins8080217. Toxins (Basel). 2016. PMID: 27463727 Free PMC article.
Cited by
-
Cloning, expression and characterization of recombinant exotoxin A-flagellin fusion protein as a new vaccine candidate against Pseudomonas aeruginosa infections.Iran Biomed J. 2013;17(1):1-7. doi: 10.6091/ibj.22.2012. Iran Biomed J. 2013. PMID: 23279828 Free PMC article.
-
A novel bispecific immunotoxin delivered by human bone marrow-derived mesenchymal stem cells to target blood vessels and vasculogenic mimicry of malignant gliomas.Drug Des Devel Ther. 2015 Jun 11;9:2947-59. doi: 10.2147/DDDT.S79475. eCollection 2015. Drug Des Devel Ther. 2015. Retraction in: Drug Des Devel Ther. 2021 Sep 02;15:3733-3734. doi: 10.2147/DDDT.S336973. PMID: 26089644 Free PMC article. Retracted.
-
Tumor-Specific Induction of the Intrinsic Apoptotic Pathway-A New Therapeutic Option for Advanced Prostate Cancer?Front Oncol. 2019 Jul 2;9:590. doi: 10.3389/fonc.2019.00590. eCollection 2019. Front Oncol. 2019. PMID: 31312616 Free PMC article. No abstract available.
-
Structural complementation of the catalytic domain of pseudomonas exotoxin A.J Mol Biol. 2014 Feb 6;426(3):645-55. doi: 10.1016/j.jmb.2013.11.002. Epub 2013 Nov 8. J Mol Biol. 2014. PMID: 24211469 Free PMC article.
-
Soluble Cytoplasmic Expression and Purification of Immunotoxin HER2(scFv)-PE24B as a Maltose Binding Protein Fusion.Int J Mol Sci. 2021 Jun 17;22(12):6483. doi: 10.3390/ijms22126483. Int J Mol Sci. 2021. PMID: 34204265 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
