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.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADP Ribose Transferases / chemistry*
  • ADP Ribose Transferases / immunology*
  • ADP Ribose Transferases / pharmacology
  • Bacterial Toxins / chemistry*
  • Bacterial Toxins / immunology*
  • Bacterial Toxins / pharmacology
  • Exotoxins / chemistry*
  • Exotoxins / immunology*
  • Exotoxins / pharmacology
  • Humans
  • Immunotoxins / chemistry*
  • Immunotoxins / immunology*
  • Immunotoxins / pharmacology
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Protein Conformation
  • Pseudomonas aeruginosa / metabolism
  • Pseudomonas aeruginosa / pathogenicity
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • Virulence Factors / chemistry*
  • Virulence Factors / immunology*
  • Virulence Factors / pharmacology

Substances

  • Bacterial Toxins
  • Exotoxins
  • Immunotoxins
  • Recombinant Fusion Proteins
  • Virulence Factors
  • ADP Ribose Transferases
  • toxA protein, Pseudomonas aeruginosa