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

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.

• Authors: J M Wu, B Wu, A Miagkov, R N Adams, D B Drachman
• Journal: Cellular immunology (Cell Immunol) Vol. 208 Issue 2 Pg. 137-47 (Mar 15 2001) ISSN: 0008-8749 [Print] Netherlands
• PMID: 11333146 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• Adaptor Proteins, Signal Transducing
• Antigens, CD
• Autoantigens
• Carrier Proteins
• Fadd protein, mouse
• Fadd protein, rat
• Fas Ligand Protein
• Fas-Associated Death Domain Protein
• Fasl protein, mouse
• Faslg protein, rat
• Lysosomal-Associated Membrane Protein 1
• Lysosome-Associated Membrane Glycoproteins
• Membrane Glycoproteins
• Receptors, Cholinergic
• Recombinant Fusion Proteins
• fas Receptor

Topics

• Adaptor Proteins, Signal Transducing
• Animals
• Antigen-Presenting Cells (immunology)
• Antigens, CD (genetics, immunology)
• Autoantigens (genetics, immunology)
• Carrier Proteins (genetics, immunology)
• Cell Line
• Fas Ligand Protein
• Fas-Associated Death Domain Protein
• Female
• Gene Expression
• Genetic Vectors
• Immunotherapy
• Lysosomal-Associated Membrane Protein 1
• Lysosome-Associated Membrane Glycoproteins
• Membrane Glycoproteins (genetics, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred MRL lpr
• Myasthenia Gravis, Autoimmune, Experimental (immunology, therapy)
• Rats
• Rats, Inbred Lew
• Receptors, Cholinergic (genetics, immunology)
• Recombinant Fusion Proteins (genetics, immunology)
• T-Lymphocytes (immunology)
• Tumor Cells, Cultured
• Vaccinia virus
• fas Receptor (immunology)