Frontiers in Neurology (Mar 2021)
Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein–Barr Virus-Specific T Cell Therapy
- Zara A. Ioannides,
- Zara A. Ioannides,
- Zara A. Ioannides,
- Peter A. Csurhes,
- Peter A. Csurhes,
- Nanette L. Douglas,
- Nanette L. Douglas,
- Nanette L. Douglas,
- Gem Mackenroth,
- Gem Mackenroth,
- Gem Mackenroth,
- Andrew Swayne,
- Andrew Swayne,
- Andrew Swayne,
- Kate M. Thompson,
- Kate M. Thompson,
- Tracey J. Hopkins,
- Kerryn A. Green,
- Kerryn A. Green,
- Stefan Blum,
- Stefan Blum,
- Stefan Blum,
- Kaye D. Hooper,
- Kaye D. Hooper,
- Kaye D. Hooper,
- Kerstin H. Wyssusek,
- Kerstin H. Wyssusek,
- Alan Coulthard,
- Alan Coulthard,
- Michael P. Pender,
- Michael P. Pender
Affiliations
- Zara A. Ioannides
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Zara A. Ioannides
- Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
- Zara A. Ioannides
- The University of Queensland Centre for Clinical Research, Herston, QLD, Australia
- Peter A. Csurhes
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Peter A. Csurhes
- The University of Queensland Centre for Clinical Research, Herston, QLD, Australia
- Nanette L. Douglas
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Nanette L. Douglas
- Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
- Nanette L. Douglas
- The University of Queensland Centre for Clinical Research, Herston, QLD, Australia
- Gem Mackenroth
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Gem Mackenroth
- Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
- Gem Mackenroth
- The University of Queensland Centre for Clinical Research, Herston, QLD, Australia
- Andrew Swayne
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Andrew Swayne
- Mater Centre for Neurosciences, Mater Hospital, Brisbane, QLD, Australia
- Andrew Swayne
- Neurology Department, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
- Kate M. Thompson
- Department of Psychology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
- Kate M. Thompson
- School of Psychology, The University of Queensland, Brisbane, QLD, Australia
- Tracey J. Hopkins
- Internal Medicine Day Treatment Unit, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
- Kerryn A. Green
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Kerryn A. Green
- Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
- Stefan Blum
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Stefan Blum
- Mater Centre for Neurosciences, Mater Hospital, Brisbane, QLD, Australia
- Stefan Blum
- Neurology Department, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
- Kaye D. Hooper
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Kaye D. Hooper
- Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
- Kaye D. Hooper
- The University of Queensland Centre for Clinical Research, Herston, QLD, Australia
- Kerstin H. Wyssusek
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Kerstin H. Wyssusek
- Department of Anesthesia and Perioperative Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
- Alan Coulthard
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Alan Coulthard
- 0Department of Medical Imaging, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
- Michael P. Pender
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Michael P. Pender
- Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
- DOI
- https://doi.org/10.3389/fneur.2021.652811
- Journal volume & issue
-
Vol. 12
Abstract
Background: Increasing evidence indicates a role for Epstein–Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the central nervous system because of defective cytotoxic CD8+ T cell immunity. We have previously reported results of a phase I clinical trial of autologous EBV-specific T cell therapy in MS 6 months after treatment.Objective: To investigate longer-term outcomes in MS patients who received autologous EBV-specific T cell therapy.Methods: We assessed participants 2 and 3 years after completion of T cell therapy.Results: We collected data from all 10 treated participants at year 2 and from 9 participants at year 3. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year 2, including reduced fatigue in three participants, and reduced Expanded Disability Status Scale score in two participants. Three participants experienced a sustained improvement in at least some symptoms at year 3. More sustained improvement was associated with higher EBV-specific CD8+ T cell reactivity in the administered T cell product.Conclusion: Autologous EBV-specific T cell therapy is well-tolerated, and some degree of clinical improvement can be sustained for up to 3 years after treatment.
Keywords
- B cell
- CD8+ T cell
- disease-modifying therapy
- Epstein-Barr virus
- progressive multiple sclerosis
- T cell therapy
