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

J. M. Wu, B. Wu, A. Miagkov, R. N. Adams, D. B. Drachman

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)137-147
Number of pages11
JournalCellular Immunology
Volume208
Issue number2
DOIs
StatePublished - Mar 15 2001

Keywords

  • Antigen presenting cells
  • Autoimmune disease
  • Fas ligand
  • Gene transfer
  • Immunotherapy
  • LAMP1
  • Myasthenia gravis
  • Vaccinia virus vector

ASJC Scopus subject areas

  • Immunology

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