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Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis.
- Source :
-
JCI insight [JCI Insight] 2018 Nov 15; Vol. 3 (22). Date of Electronic Publication: 2018 Nov 15. - Publication Year :
- 2018
-
Abstract
- Background: Increasing evidence indicates a role for EBV in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8+ T cell immunity. We sought to determine the feasibility and safety of treating progressive MS patients with autologous EBV-specific T cell therapy.<br />Methods: An open-label phase I trial was designed to treat 5 patients with secondary progressive MS and 5 patients with primary progressive MS with 4 escalating doses of in vitro-expanded autologous EBV-specific T cells targeting EBV nuclear antigen 1, latent membrane protein 1 (LMP1), and LMP2A. Following adoptive immunotherapy, we monitored the patients for safety and clinical responses.<br />Results: Of the 13 recruited participants, 10 received the full course of T cell therapy. There were no serious adverse events. Seven patients showed improvement, with 6 experiencing both symptomatic and objective neurological improvement, together with a reduction in fatigue, improved quality of life, and, in 3 patients, reduced intrathecal IgG production. All 6 patients receiving T cells with strong EBV reactivity showed clinical improvement, whereas only 1 of the 4 patients receiving T cells with weak EBV reactivity showed improvement (P = 0.033, Fisher's exact test).<br />Conclusion: EBV-specific adoptive T cell therapy was well tolerated. Clinical improvement following treatment was associated with the potency of EBV-specific reactivity of the administered T cells. Further clinical trials are warranted to determine the efficacy of EBV-specific T cell therapy in MS.<br />Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12615000422527.<br />Funding: MS Queensland, MS Research Australia, Perpetual Trustee Company Ltd., and donations from private individuals who wish to remain anonymous.
- Subjects :
- Adult
Aged
Epstein-Barr Virus Nuclear Antigens immunology
Female
Humans
Immunotherapy, Adoptive
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis diagnostic imaging
Multiple Sclerosis virology
Treatment Outcome
Viral Matrix Proteins immunology
Herpesvirus 4, Human immunology
Multiple Sclerosis therapy
T-Lymphocytes immunology
T-Lymphocytes transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 3
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 30429369
- Full Text :
- https://doi.org/10.1172/jci.insight.124714