Use of ribosome-inactivating proteins from Sambucus for the construction of immunotoxins and conjugates for cancer therapy

Toxins (Basel). 2011 May;3(5):420-41. doi: 10.3390/toxins3050420. Epub 2011 Apr 29.

Abstract

The type 2 ribosome-inactivating proteins (RIPs) isolated from some species belonging to the Sambucus genus, have the characteristic that although being even more active than ricin inhibiting protein synthesis in cell-free extracts, they lack the high toxicity of ricin and related type 2 RIPs to intact cells and animals. This is due to the fact that after internalization, they follow a different intracellular pathway that does not allow them to reach the cytosolic ribosomes. The lack of toxicity of type 2 RIPs from Sambucus make them good candidates as toxic moieties in the construction of immunotoxins and conjugates directed against specific targets. Up to now they have been conjugated with either transferrin or anti-CD105 to target either transferrin receptor- or endoglin-overexpressing cells, respectively.

Keywords: ribosome-inactivating proteins; Sambucus; endoglin (CD105); immunotoxin; transferrin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Survival / drug effects
  • HeLa Cells
  • Humans
  • Immunotoxins / chemistry
  • Immunotoxins / pharmacology*
  • Immunotoxins / therapeutic use
  • Lethal Dose 50
  • Models, Molecular
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Protein Conformation
  • Ribosome Inactivating Proteins, Type 2 / chemistry*
  • Ribosome Inactivating Proteins, Type 2 / genetics
  • Ribosome Inactivating Proteins, Type 2 / isolation & purification
  • Ribosome Inactivating Proteins, Type 2 / pharmacology*
  • Sambucus / chemistry*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Immunotoxins
  • Ribosome Inactivating Proteins, Type 2