Interleukin 2 pseudomonas exotoxin (IL2-PE66(4)Glu) chimeric protein kills B cells from patients with Myasthenia gravis.
IL2-PE66(4)Glu is a chimeric cytotoxin consisting of interleukin 2 (IL2) fused to a mutant form of Pseudomonas exotoxin (PE66(4)Glu). The chimeric cytotoxin has been previously shown to be extremely toxic to both phytohemagglutinin blasts and mixed leukocyte reaction blasts prepared from monkey and human lymphocytes. To explore the possible clinical utility of IL2-PE66(4)Glu for autoimmune diseases, particularly in which B cells are involved, we tested fresh B cells from patients with myasthenia gravis for sensitivity to this chimeric cytotoxin. Seventy-six percent (16 of 21) of the B cells tested were markedly sensitive to IL2-PE66(4)Glu-mediated cytotoxicity, with inhibition of protein synthesis ranging from 20 to 92%. B cells from control donors were much less sensitive to IL2-PE66(4)Glu cytotoxicity. Moreover, a control protein lacking IL2 as the targeting moiety of the chimera had no effect toward all B cells tested, thus establishing its specific activity. Our results suggest that IL2-PE66(4)Glu could be an effective tool for selective targeted immunotherapy of myasthenia gravis patients.
Steinberger
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I
Department of Cellular Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Brenner
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T
Lorberboum-Galski
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H
D036002:ADP Ribose Transferases; D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D001427:Bacterial Toxins; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D005098:Exotoxins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C065698:interleukin 2-PE66(4Glu) protein, recombinant