Disability Improvement and Possible Remyelination in Progressive Multiple Sclerosis After Novel T-Cell Treatment Targeting Latent Epstein-Barr Virus

Treatment with allogeneic T cells, targeting B cells and plasma cells containing Epstein-Barr virus (ATA188; Atara, South San Francisco, CA), resulted in sustained disability improvement (SDI) for 9 of 18 individuals with progressive multiple sclerosis (PMS). Further, SDI was sustained for up to 33 months in 7 participants. Those who received higher doses of EBV-reactive T cells were more likely to have SDI, showing a dose-response to the treatment. SDI was defined as improved score on the Expanded Disability Status Score (n=7) or the timed 25-foot walk test (n=2). 

Notably, a potential biomarker of remyelination, the magnetic transfer ratio (MTR), suggested that in those who achieved SDI, myelin density increased. At 1 year posttreatment, all 7 individuals who achieved EDSS score improvement also had increased MTR scores in both T2-enhancing lesions and overall brain compared with those without EDSS improvement. 

Dr. Bridget Bagert, MD, director, Ochsner Multiple Sclerosis Center, New Orleans, LA and a site investigator for the study explained, "Although larger randomized controlled trials are needed to confirm these results, this is potentially the first treatment to reverse disability rather than simply slow progression. That is a truly different outcome from what we have seen with other treatments to date and could be a remarkable advance in MS treatment. The dose-response and correlation of an objective biomarker observed in those who achieved SDI are particularly encouraging. Today, there is a new reason to have increased hope for our patients with PMS."

This intravenously administered T-cell treatment is allogeneic, available "off the shelf," and matched to the individual patient via human leukocyte antigen (HLA) markers. As a result, no immunosuppression before or after transplant is required. Treatment has been well tolerated with only 1 possibly treatment-related MS relapse (grade 3) and no dose-limiting toxicities, cytokine release syndrome, graft-versus-host disease, or infusion-related reactions observed.

A phase 2 trial (NCT03283826), known as EMBOLD, is currently enrolling participants with primary or secondary PMS.

These data were presented at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) taking place virtually October 13-15, 2021.