A novel antigen-toxin chimeric protein: myelin basic protein-pseudomonas exotoxin (MBP-PE 40) for treatment of experimental autoimmune encephalomyelitis.
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.
Brenner
T
T
Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
Steinberger
I
I
Soffer
D
D
Beraud
E
E
Ben-Nun
A
A
Lorberboum-Galski
H
H
D036002:ADP Ribose Transferases; D000208:Acute Disease; D000818:Animals; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D005098:Exotoxins / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D004676:Myelin Basic Protein / Q000627:therapeutic use* / Q000633:toxicity; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D005098:Exotoxins; D000922:Immunotoxins; C121159:MBP-PE40; D004676:Myelin Basic Protein; D011993:Recombinant Fusion Proteins; D036002:ADP Ribose Transferases