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 Citations (Scopus)

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
JournalClinical Immunology
Volume99
Issue number2
StatePublished - 2001

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Autoimmune Experimental Myasthenia Gravis
Cholinergic Receptors
Antigen-Presenting Cells
Fas Ligand Protein
Immunotherapy
T-Lymphocytes
Myasthenia Gravis
Antigens
Genetic Engineering
Vaccinia virus
Genes
Autoimmune Diseases
Cell Culture Techniques
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cell Biology

Cite this

Wu, J. M., Wu, B., Miagkov, A., Adams, R. N., & Drachman, D. B. (2001). Specific immunotherapy of experimental myasthenia gravis in vitro: The "Guided Missile" strategy. Clinical Immunology, 99(2), 137-147.

Specific immunotherapy of experimental myasthenia gravis in vitro : The "Guided Missile" strategy. / Wu, J. M.; Wu, B.; Miagkov, A.; Adams, R. N.; Drachman, D. B.

In: Clinical Immunology, Vol. 99, No. 2, 2001, p. 137-147.

Research output: Contribution to journalArticle

Wu, JM, Wu, B, Miagkov, A, Adams, RN & Drachman, DB 2001, 'Specific immunotherapy of experimental myasthenia gravis in vitro: The "Guided Missile" strategy', Clinical Immunology, vol. 99, no. 2, pp. 137-147.
Wu, J. M. ; Wu, B. ; Miagkov, A. ; Adams, R. N. ; Drachman, D. B. / Specific immunotherapy of experimental myasthenia gravis in vitro : The "Guided Missile" strategy. In: Clinical Immunology. 2001 ; Vol. 99, No. 2. pp. 137-147.
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