INTERLEUKIN-2 PSEUDOMONAS EXOTOXIN (IL2-PE66(4GLU)) CHIMERIC PROTEIN KILLS B-CELLS FROM PATIENTS WITH MYASTHENIA-GRAVIS

IL2-PE66(4Glu) is a chimeric cytotoxin consisting of interleukin 2 (IL 2) fused to a mutant form of Pseudomonas exotoxin (PE66(4Glu)). The ch imeric cytotoxin has been previously shown to be extremely toxic to bo th phytohemagglutinin blasts and mixed leukocyte reaction blasts prepa red from monkey and human lymphocytes. To explore the possible clinica l utility of IL2-PE66(4Glu) for autoimmune diseases, particularly in w hich 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 t o IL2-PE66(4Glu)-mediated cytotoxicity, with inhibition of protein syn thesis ranging from 20 to 92%. B cells from control donors were much l ess sensitive to IL2-PE66(4Glu) cytotoxicity. Moreover, a control prot ein lacking IL2 as the targeting moiety of the chimera had no effect t oward all B cells tested, thus establishing its specific activity. Our results suggest that IL2-PE66(4Glu) could be an effective tool for se lective targeted immunotherapy of myasthenia gravis patients. (C) 1996 Academic Press, Inc.