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Related Experiment Video

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Establishment of Epstein-Barr Virus Growth-transformed Lymphoblastoid Cell Lines
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Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis.

Michael P Pender1,2,3, Peter A Csurhes1,4, Corey Smith3

  • 1Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

JCI Insight
|November 16, 2018
PubMed
Summary

Autologous Epstein-Barr virus (EBV)-specific T cell therapy is a safe treatment for progressive multiple sclerosis (MS). Clinical improvements in MS patients correlated with the strength of EBV reactivity in the T cells used.

Keywords:
Autoimmune diseasesClinical TrialsNeuroscienceT cells

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Area of Science:

  • Immunology
  • Neurology
  • Cell Therapy

Background:

  • Epstein-Barr virus (EBV) is increasingly implicated in multiple sclerosis (MS) pathogenesis.
  • Defective cytotoxic CD8+ T cell immunity may lead to EBV-infected autoreactive B cells accumulating in the central nervous system (CNS).

Purpose of the Study:

  • To assess the feasibility and safety of autologous EBV-specific T cell therapy for progressive MS.
  • To evaluate clinical responses in patients with progressive MS receiving this novel immunotherapy.

Main Methods:

  • An open-label, phase I clinical trial was conducted.
  • Ten patients with progressive MS (5 secondary progressive, 5 primary progressive) received escalating doses of in vitro-expanded autologous EBV-specific T cells.
  • T cells targeted EBV nuclear antigen 1, latent membrane protein 1 (LMP1), and LMP2A.

Main Results:

  • Ten of 13 recruited participants completed the T cell therapy course without serious adverse events.
  • Seven patients demonstrated clinical improvement, with 6 experiencing both symptomatic and objective neurological gains.
  • Improvements included reduced fatigue, enhanced quality of life, and decreased intrathecal IgG production in 3 patients. Strong EBV reactivity of T cells correlated with clinical improvement (P = 0.033).

Conclusions:

  • Autologous EBV-specific T cell therapy is well-tolerated in progressive MS patients.
  • Clinical benefits are associated with the potency of EBV-specific T cell reactivity.
  • Further trials are necessary to establish the efficacy of this therapeutic approach for MS.