Interleukin 2-Bax: a novel prototype of human chimeric proteins for targeted therapy

FEBS Lett. 1999 Aug 27;457(2):271-6. doi: 10.1016/s0014-5793(99)01050-9.

Abstract

During the past few years many chimeric proteins have been developed to target and kill cells expressing specific surface molecules. Generally, these molecules carry a bacterial or plant toxin that destroys the unwanted cells. The major obstacle in the clinical application of such chimeras is their immunogenicity and non-specific toxicity. We have developed a new generation of chimeric proteins, taking advantage of apoptosis-inducing proteins, such as the human Bax protein, as novel killing components. The first prototype chimeric protein, IL2-Bax, directed toward IL2R-expressing cells, was constructed, expressed in Escherichia coli and partially purified. IL2-Bax increased the population of apoptotic cells in a variety of target T cell lines, as well as in human fresh PHA-activated lymphocytes, in a dose-dependent manner and had no effect on cells lacking IL2R expression. The IL2-Bax chimera represents an innovative approach for constructing chimeric proteins comprising a molecule that binds a specific cell type and an apoptosis-inducing protein. Such new chimeric proteins could be used for targeted treatment of human diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • Cell Division / drug effects
  • Drug Delivery Systems
  • Flow Cytometry
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / pharmacology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2*
  • Receptors, Interleukin-2 / biosynthesis
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / pharmacology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • Interleukin-2
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • bcl-2-Associated X Protein