PMID: 2492102Jan 1, 1989Paper

Chimeric cytotoxin IL2-PE40 delays and mitigates adjuvant-induced arthritis in rats

Proceedings of the National Academy of Sciences of the United States of America
J P CaseI Pastan

Abstract

Adjuvant arthritis in rats is a T-cell dependent "autoimmune" disease with close similarities to several forms of human arthritis. Injection of mycobacterial adjuvant leads to T-cell activation and proliferation, processes in which the de novo expression of the interleukin 2 (IL-2) receptor plays a pivotal role. The subsequent massive mononuclear cell infiltration of the joints ultimately results in complete joint destruction. Because activation of the helper/inducer subset of T lymphocytes is critical to the establishment of disease, we reasoned that IL2-PE40, a cytotoxic IL-2-Pseudomonas exotoxin fusion protein that targets the membrane-penetration and ADP-ribosylation domains of the toxin to cells bearing the IL-2 receptor, would be an effective and specific therapy. Adjuvant-injected rats were randomized to treatment with IL2-PE40, phosphate-buffered saline, or either of two control proteins related to IL2-PE40 but lacking either the receptor-binding moiety or an enzymatically active toxin domain and previously demonstrated to lack cytotoxicity in vitro. Intraperitoneal IL2-PE40 given before the establishment of overt clinical disease proved an effective and specific modifier of adjuvant arthritis by clinical, histological,...Continue Reading

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Citations

May 1, 1995·Journal of Neuroscience Research·N L Nadon, I D Duncan
Jan 1, 1992·Immunologic Research·H A VerheulE S Bos
Nov 1, 1995·Journal of the Neurological Sciences·I SteinbergerH Lorberboum-Galski
Apr 1, 1992·International Journal of Immunopharmacology·R J KreitmanI Pastan
Jul 1, 1996·Research in Immunology·H AmitalY Shoenfeld
Apr 1, 1989·Current Opinion in Immunology·O PankewyczV E Kelley
Jun 6, 2000·Advanced Drug Delivery Reviews·I Pastan, R J Kreitman
Feb 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·H Lorberboum-GalskiI Pastan
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·V K ChaudharyI Pastan
Nov 1, 1990·Seminars in Immunology·T B StromJ R Murphy
Jul 5, 2005·Expert Opinion on Investigational Drugs·R J Kreitman
Sep 30, 2005·International Journal of Experimental Pathology·Michael J SegelRaphael Breuer
Apr 28, 1989·Biochemical and Biophysical Research Communications·D A LappiA Baird
Jan 1, 1990·Progress in Growth Factor Research·D A Lappi, A Baird
Feb 1, 1995·Current Eye Research·D BenEzraH Lorberboum-Galski
Jul 1, 1993·Medicinal Research Reviews·M WilliamsG L Neil
Apr 6, 2001·International Journal of Cancer. Journal International Du Cancer·A Ben-YehudahH Lorberboum-Galski
Dec 30, 1991·Annals of the New York Academy of Sciences·T B StromJ R Murphy

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