Frontiers in Immunology (Apr 2017)

Use of Lentiviral Particles As a Cell Membrane-Based mFasL Delivery System for In Vivo Treatment of Inflammatory Arthritis

  • Mario Mellado,
  • José M. Rodríguez-Frade,
  • Anabel Guedán,
  • Pilar Lucas,
  • Laura Martínez-Muñoz,
  • Ricardo Villares,
  • Gabriel Criado,
  • Dimitri Balomenos,
  • Hugh T. Reyburn

DOI
https://doi.org/10.3389/fimmu.2017.00460
Journal volume & issue
Vol. 8

Abstract

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During budding, lentiviral particles (LVP) incorporate cell membrane proteins in the viral envelope. We explored the possibility of harnessing this process to generate LVP-expressing membrane proteins of therapeutic interest and studied the potential of these tools to treat different pathologies. Fas-mediated apoptosis is central to the maintenance of T cell homeostasis and prevention of autoimmune processes. We prepared LVP that express murine FasL on their surface. Our data indicate that mFasL-bearing LVP induce caspase 3 and 9 processing, cytochrome C release, and significantly more cell death than control LVP in vitro. This cytotoxicity is blocked by the caspase inhibitor Z-VAD. Analysis of the application of these reagents for the treatment of inflammatory arthritis in vivo suggests that FasL-expressing LVP could be useful for therapy in autoimmune diseases such as rheumatoid arthritis, where there is an excess of Fas-expressing activated T cells in the joint. LVP could be a vehicle not only for mFasL but also for other membrane-bound proteins that maintain their native conformation and might mediate biological activities.

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