Published October 15, 2020 - More info
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. 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. 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). 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. TRIAL REGISTRATION. Australian New Zealand Clinical Trials Registry, ACTRN12615000422527. FUNDING. MS Queensland, MS Research Australia, Perpetual Trustee Company Ltd., and donations from private individuals who wish to remain anonymous.
Michael P. Pender, Peter A. Csurhes, Corey Smith, Nanette L. Douglas, Michelle A. Neller, Katherine K. Matthews, Leone Beagley, Sweera Rehan, Pauline Crooks, Tracey J. Hopkins, Stefan Blum, Kerryn A. Green, Zara A. Ioannides, Andrew Swayne, Blake T. Aftab, Kaye D. Hooper, Scott R. Burrows, Kate M. Thompson, Alan Coulthard, Rajiv Khanna
Original citation: JCI Insight. 2018;3(22):e124714. https://doi.org/10.1172/jci.insight.124714
Citation for this corrigendum: JCI Insight. 2020;5(20):e144624. https://doi.org/10.1172/jci.insight.144624
During the preparation of this manuscript, errors relating to data for BVMT-TL, BVMT-DR, PASAT3, and PASAT2 were inadvertently introduced into Figure 3C. Several of the data points have changed, but there are only minimal changes in the mean values and standard deviations. In addition, in Results, in the section Clinical outcomes following T cell therapy, the P value for PASAT3 is incorrect. However, after applying Bonferroni’s correction for multiple comparisons, the new P value still does not reach significance. The correct sentence and figure part are below. The online HTML and PDF versions of the manuscript have been updated to reflect these changes.
Statistically significant, or nearly significant, increases in attainment were observed at week 27 across two measures, the Controlled Oral Word Association Test (COWAT, a verbal fluency test) and the Paced Auditory Serial Addition Test (PASAT3, a working memory/processing speed task) (P = 0.074 and P = 0.0356 respectively, paired 2-tailed t test); however, after applying the Bonferroni correction for multiple comparisons, these P values no longer reached significance.
The authors regret the errors.
See the related article at Epstein-Barr virus–specific T cell therapy for progressive multiple sclerosis.