Specific immunotherapy of experimental myasthenia gravis in vitro: the "guided missile" strategy

Cellular Immunology
J M WuD B Drachman

Abstract

We describe a strategy for specific immunotherapy of myasthenia gravis (MG) based on genetic engineering of antigen presenting cells (APCs) to present the autoantigen acetylcholine receptor (AChR) and express the "warhead" Fas ligand (FasL). For transduction of APCs we prepared recombinant attenuated vaccinia virus vectors carrying the following three gene constructs: (i) AChR fused to LAMP1 to present AChR and target AChR-specific T cells; (ii) FasL to eliminate the targeted T cells; and (iii) truncated FADD to protect APCs from self-destruction by FasL. The engineered APCs effectively expressed the genes of interest and killed AChR-specific T cells in culture by the Fas/FasL pathway. T cells specific for an unrelated antigen were spared. Our in vitro demonstration that engineered APCs target and kill antigen-specific T cells represents a promising novel strategy for specific immunotherapy of MG and other autoimmune diseases.

References

Dec 25, 1976·Lancet·A J Pinching, D K Peters
Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
May 18, 1978·The New England Journal of Medicine·D B DrachmanG J Hoffman
Jan 20, 1977·The New England Journal of Medicine·K V ToykaI Kao
Jan 1, 1976·Annals of the New York Academy of Sciences·V A LennonM E Seybold
Nov 1, 1990·Virology·S J GoebelE Paoletti
Jan 1, 1987·Annals of the New York Academy of Sciences·R HohlfeldS J Tzartos
Jun 1, 1989·Journal of Autoimmunity·J Newsom-DavisJ B Rothbard
Jan 1, 1988·Advances in Immunology·J LindstromY Fujii
Nov 1, 1973·Archives of Biochemistry and Biophysics·M E Eldefrawi, A T Eldefrawi
Dec 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·M MackettB Moss
Aug 1, 1995·Current Opinion in Cell Biology·I MellmanS Amigorena
Dec 1, 1993·The Journal of Experimental Medicine·M R AldersonD H Lynch
Mar 10, 1995·Science·S Nagata, P Golstein
Jun 21, 1993·Annals of the New York Academy of Sciences·L MoiolaB M Conti-Tronconi
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J DrappaK B Elkon
Oct 1, 1994·International Immunology·T TakahashiS Nagata
Jun 21, 1993·Annals of the New York Academy of Sciences·S SchönbeckH Wekerle
Jul 1, 1993·Immunology Today·M P ProttiB M Conti-Tronconi
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·T C WuD M Pardoll
Oct 4, 1996·Science·L H Boise, C B Thompson
Jan 7, 1998·The Journal of Experimental Medicine·B WongY Choi
Jan 22, 1998·Clinical Immunology and Immunopathology·W M Ridgway, C G Fathman
Jan 22, 1998·Clinical Immunology and Immunopathology·B YangD B Drachman
Jan 8, 1999·Journal of Autoimmunity·D NavaneethamB M Conti-Fine

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Citations

Feb 24, 2004·Journal of Hematotherapy & Stem Cell Research·Daniel B Drachman
Nov 3, 2006·The Journal of Clinical Investigation·Bianca M Conti-FineHenry J Kaminski
Jun 24, 2008·Annals of the New York Academy of Sciences·Mario LosenMarc H De Baets
May 4, 2010·Annals of Neurology·Hartmut Wekerle, Reinhard Hohlfeld
Jul 18, 2008·Handbook of Clinical Neurology·Daniel B Drachman
Nov 19, 2002·Journal of Neurobiology·Jon Lindstrom
Feb 5, 2005·The Journal of Gene Medicine·Aude BonehillKris Thielemans
Mar 2, 2010·Autoimmunity·George LagoumintzisSocrates J Tzartos

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