Immunotoxins and cytokine toxin fusion proteins

Ann N Y Acad Sci. 1991 Dec 30;636:233-50. doi: 10.1111/j.1749-6632.1991.tb33455.x.

Abstract

Paul Ehrlich first suggested the simple and elegant concept of creating specific cell toxins or "magic bullets" through the fusion of cell-specific antibodies and toxins. In practice it has proven difficult to create safe and effective "magic bullets." In the past several years, several immunotoxins have been applied to clinical testing. These immunotoxins have been created by the biochemical coupling of cell- or lineage-specific monoclonal antibodies to plant toxins or fragments thereof. These immunotoxins have been used to treat bone marrow transplant recipients and patients with autoimmune disorders. In recent years, another strategy has also been pursued to create hybrid toxins. Rather than use antibodies as the targeting moiety, cytokines have been used to target a select population of cells bearing a high copy number of receptors for the specific cytokine. Rather than biochemically couple a cytokine to the toxin, the cytokine and toxin are fused by a peptide bond established via genetic engineering. A prototype IL-2 diphtheria toxin-related fusion protein is now being tested in the clinic for treatment of hematopoietic malignancies and autoimmune disorders.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Bacterial Toxins / administration & dosage
  • Diphtheria Toxin / administration & dosage*
  • Humans
  • Immunotoxins / administration & dosage*
  • Interleukin-2 / administration & dosage*
  • Recombinant Fusion Proteins / therapeutic use*
  • Shiga Toxins

Substances

  • Bacterial Toxins
  • DAB(486)-interleukin 2
  • Diphtheria Toxin
  • Immunotoxins
  • Interleukin-2
  • Recombinant Fusion Proteins
  • Shiga Toxins