New Life for Immunotoxin Cancer Therapy

Clin Cancer Res. 2016 Mar 1;22(5):1055-8. doi: 10.1158/1078-0432.CCR-15-1623. Epub 2015 Oct 13.

Abstract

Immunotoxins are targeted anticancer therapeutics that kill cancer cells using a cytotoxic bacterial toxin payload. Their development for use in solid tumor malignancies was delayed due to issues with their immunogenicity and limited therapeutic window. However, new research has rejuvenated the field. Coadministration with a lymphocyte-depleting regimen of pentostatin and cyclophosphamide can delay antidrug antibody formation, increasing the number of treatment cycles that patients can receive and resulting in durable responses in heavily pretreated patients. In addition, a new generation of immunotoxin molecules with reduced immunogenicity and nonspecific toxicity has been developed through protein engineering techniques, and one has recently entered the clinic. In preclinical studies in mouse models, these new agents are effective against many tumor types as single agents, and also produce synergistic antitumor responses in combination with chemotherapy. These new immunotoxins have renewed excitement in the field and may prove a promising addition to the targeted therapy repertoire.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • ADP Ribose Transferases / genetics
  • ADP Ribose Transferases / immunology
  • ADP Ribose Transferases / therapeutic use
  • Animals
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Neoplasm / genetics
  • Antibodies, Neoplasm / immunology
  • Antibodies, Neoplasm / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Bacterial Toxins / genetics
  • Bacterial Toxins / immunology
  • Bacterial Toxins / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Disease Models, Animal
  • Exotoxins / genetics
  • Exotoxins / immunology
  • Exotoxins / therapeutic use
  • Humans
  • Immunotherapy*
  • Lymphocytes / drug effects
  • Mesothelioma / drug therapy*
  • Mesothelioma / genetics
  • Mesothelioma / pathology
  • Mice
  • Pentostatin / therapeutic use
  • Pseudomonas aeruginosa Exotoxin A
  • Virulence Factors / genetics
  • Virulence Factors / immunology
  • Virulence Factors / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Bacterial Toxins
  • Exotoxins
  • SS1(dsFv)PE38
  • Virulence Factors
  • Pentostatin
  • Cyclophosphamide
  • ADP Ribose Transferases