Challenges for Therapeutic Application of Pseudomonas Exotoxin-Based Immunotoxins

Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 6)


Immunotoxins are therapeutic molecules that belong to a class of biopharmaceuticals called “Armed antibodies”. Immunotoxins are based on very potent toxins of bacterial or plant origin that lack target-cell specificity. To make them target-cell-specific, the non-specific cell binding domains of the original toxins are replaced with a target-cell-specific binding protein, in most cases a monoclonal antibody or a recombinant antibody fragment. The most clinically-advanced immunotoxins are currently being evaluated in phase II and III clinical studies. Like other targeted and non-targeted therapeutics, immunotoxins too suffer from several limitations that may hinder their therapeutic efficacy. Such limitations include, but are not limited to immunogenicity, modification of the extracellular target to which the targeting antibody binds, modification of the intracellular target upon which the toxin acts to cause cell growth inhibition, and insufficient potency as single agents and off-target toxicity, where non-target cells and organs are affected by the immunotoxin, severely impairing its therapeutic index. This chapter is devoted to a group of immunotoxins in which the toxic moiety is derived from exotoxin A (PE) of the bacterium Pseudomonas aeruginosa. The limitations to the efficacy of PE-based immunotoxins, as well as potential solutions for overcoming such limitations, will be presented. Chapter 2 of this book: “Resistance of tumor cells against antibody-targeted protein toxins” by Ulrich Brinkmann et al. is focused on factors that influence the sensitivity or potential resistances of cancer cells towards recombinant immunotoxins which carry truncated and/or mutated derivatives of Pseudomonas exotoxin as cytotoxic payloads.


Immunotoxin(s) Pseudomonas exotoxin A Immunotoxin Monoclonal antibody Immunogenicity De-immunization 



Antibody-drug conjugate


Antigen presenting cells


Adult T-cell leukemia


The blood brain barrier


Convection-enhanced delivery


Chronic lymphocytic leukemia


Cutaneous T-cell lymphoma


Disulfide-stabilized Fv fragment of an antibody


Diphtheria toxin; E. coli, Escherichia coli bacteria


Epidermal growth factor receptor


Glioblastoma multiforme


Hairy cell leukemia


Interleukin 13


Receptor for IL13


Interleukin 4


Receptor for IL4




LewisY carbohydrate antigen


Monoclonal antibody


Non-steroidal anti-inflammatory drugs


Peripheral blood mononuclear cells


Pancreatic ductal adenocarcinoma

PE (or ETA)

Pseudomonas exotoxin A


Polyethylene glycol


Antibody-radionuclide conjugates (radioimmunoconjugates)


Ribosome-inactivating protein


Single-chain Fv fragment of an antibody


Vascular leak syndrome


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life SciencesTel-Aviv UniversityRamat AvivIsrael

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