Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein-Barr Virus-Specific T Cell Therapy.

Autor:	Ioannides ZA; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.; The University of Queensland Centre for Clinical Research, Herston, QLD, Australia., Csurhes PA; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; The University of Queensland Centre for Clinical Research, Herston, QLD, Australia., Douglas NL; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.; The University of Queensland Centre for Clinical Research, Herston, QLD, Australia., Mackenroth G; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.; The University of Queensland Centre for Clinical Research, Herston, QLD, Australia., Swayne A; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Mater Centre for Neurosciences, Mater Hospital, Brisbane, QLD, Australia.; Neurology Department, Princess Alexandra Hospital, Woolloongabba, QLD, Australia., Thompson KM; Department of Psychology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.; School of Psychology, The University of Queensland, Brisbane, QLD, Australia., Hopkins TJ; Internal Medicine Day Treatment Unit, Royal Brisbane and Women's Hospital, Herston, QLD, Australia., Green KA; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia., Blum S; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Mater Centre for Neurosciences, Mater Hospital, Brisbane, QLD, Australia.; Neurology Department, Princess Alexandra Hospital, Woolloongabba, QLD, Australia., Hooper KD; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.; The University of Queensland Centre for Clinical Research, Herston, QLD, Australia., Wyssusek KH; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Department of Anesthesia and Perioperative Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, Australia., Coulthard A; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Department of Medical Imaging, Royal Brisbane and Women's Hospital, Herston, QLD, Australia., Pender MP; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
Jazyk:	angličtina
Zdroj:	Frontiers in neurology [Front Neurol] 2021 Mar 15; Vol. 12, pp. 652811. Date of Electronic Publication: 2021 Mar 15 (Print Publication: 2021).
DOI:	10.3389/fneur.2021.652811
Abstrakt:	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. Competing Interests: ZI: Received clinical trial support from Atara Biotherapeutics. MP: Received research grants from Atara Biotherapeutics and MS Queensland, and consultancy fees, clinical trial support, and travel support from Atara Biotherapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Ioannides, Csurhes, Douglas, Mackenroth, Swayne, Thompson, Hopkins, Green, Blum, Hooper, Wyssusek, Coulthard and Pender.)
Databáze:	MEDLINE
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