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A novel antigen-toxin chimeric protein: myelin basic protein-pseudomonas exotoxin (MBP-PE 40) for treatment of experimental autoimmune encephalomyelitis.

Abstract
Myelin basic protein (MBP), is a major component of the central nervous system (CNS) myelin. MBP can stimulate T cells that migrate into the CNS, initiating a cascade of events that result in perivascular infiltration and demyelination. EAE is an inflammatory and demyelinating autoimmune disease of the CNS that serves as a model for the human disease Multiple Sclerosis (MS). Taking advantage of the fact that EAE can be mediated by T cells, able to recognize MBP or its peptides, we developed a new approach to target anti-MBP T cells by fusing an MBP-sequence to a toxin. In the new chimeric protein, an oligonucleotide coding for the guinea pig MBP encephalitogenic moiety (residues 68-88) was fused to a cDNA encoding a truncated form of the PE gene (PE40). The chimeric gene termed MBP-PE was expressed in E. coli and highly purified. MBP-PE chimeric protein was cytotoxic to various anti-MBP T cells. Moreover, treatment with the novel MBP-toxin blocked the clinical signs of EAE as well as CNS inflammation and demyelination. A chimeric protein such as MBP-PE40 presents a novel prototype of chimeric proteins, composed of antigen/peptide-toxin, that could prove to be an efficient and specific immunotherapeutic agent for autoimmune diseases in which a known antigen is involved.
AuthorsT Brenner, I Steinberger, D Soffer, E Beraud, A Ben-Nun, H Lorberboum-Galski
JournalImmunology letters (Immunol Lett) Vol. 68 Issue 2-3 Pg. 403-10 (Jun 01 1999) ISSN: 0165-2478 [Print] Netherlands
PMID10424450 (Publication Type: Journal Article)
Chemical References
  • Exotoxins
  • Immunotoxins
  • MBP-PE40
  • Myelin Basic Protein
  • Recombinant Fusion Proteins
  • ADP Ribose Transferases
Topics
  • ADP Ribose Transferases
  • Acute Disease
  • Animals
  • Cell Line
  • Encephalomyelitis, Autoimmune, Experimental (drug therapy, pathology)
  • Exotoxins (therapeutic use, toxicity)
  • Female
  • Immunotoxins (therapeutic use)
  • Mice
  • Myelin Basic Protein (therapeutic use, toxicity)
  • Recombinant Fusion Proteins (therapeutic use)
  • T-Lymphocytes (cytology, drug effects)

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