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A guide to taming a toxin - recombinant immunotoxins constructed from Pseudomonas exotoxin A for the treatment of cancer

Journal

FEBS JOURNAL
Volume 278, Issue 23, Pages 4683-4700

Publisher

WILEY
DOI: 10.1111/j.1742-4658.2011.08182.x

Keywords

antibody conjugates; cancer therapy; intracellular trafficking; moxetumomab pasudotox; Pseudomonas exotoxin A; recombinant immunotoxins

Funding

  1. National Institutes of Health, National Cancer Institute, Center for Cancer Research
  2. MedImmune, LLC

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Pseudomonas exotoxin A (PE) is a highly toxic protein secreted by the opportunistic pathogen Pseudomonas aeruginosa. The modular structure and corresponding mechanism of action of PE make it amenable to extensive modifications that can redirect its potent cytotoxicity from disease to a therapeutic function. In combination with a variety of artificial targeting elements, such as receptor ligands and antibody fragments, PE becomes a selective agent for the elimination of specific cell populations. This review summarizes our current understanding of PE, its intoxication pathway, and the ongoing efforts to convert this toxin into a treatment for cancer.

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