Epstein-Barr virus-targeted T-cell immunotherapy for progressive MS

Off-the-shelf ATA188, an allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy, was well tolerated across all 4 dose cohorts in patients with progressive multiple sclerosis (MS) in an open-label phase 1 study. There was a possible signal of therapeutic response, with a higher proportion of patients showing sustained disability improvement with increasing dose [1].

EBV is considered a risk factor in triggering MS. Mounting evidence suggests that EBV-infected immune cells, in particular memory B cells, play an important role in propagating both relapsing and progressive forms of MS. ATA188 offers a novel treatment approach selectively targeting and eliminating EBV-infected B cells and plasma cells in the circulation and central nervous system.

A phase 1a multicentre study assessed safety and efficacy of ATA188 in patients with progressive forms of MS. Patients were treated across 4 dose-escalating cohorts, with 6 patients each in cohorts 1-3 and 7 patients in cohort 4. Across the 4 dose cohorts, ATA188 was well tolerated, with no dose-limiting toxicities or fatal adverse events. Additionally, ATA188 infusion showed no clinically meaningful effect on cytokine levels post-infusion.

Two methods to assess clinical outcomes were used. The first scale was based on Sustained Disability Improvement (SDI), a composite of improvement in Expanded Disability Status Scale (EDSS) or Timed 25-Foot Walk at consecutive time points (3 and 6 months, 6 and 12 months). All patients in cohorts 1-3 showing SDI at 6 months maintained improvement through 12 months (see Table). Additionally, there was a dose-related increase in the number of patients with SDI. The second composite scale (designed to detect early signals of efficacy) was an a priori classification of patient outcomes, incorporating 7 scales for MS symptoms, function, and disability. This scale also showed a dose-related trend of a higher proportion of patients showing favourable clinical improvement. Based on these results, the cohort 3 dose was selected for the randomised, placebo-controlled phase 1b study.

Table. Clinical outcomes and composite scale of SDI in patients receiving ATA188 [1].



m, months; SDI, sustained disability improvement.

1. Bar-Or A, et al. Abstract LB130, EAN 2020.

 



Posted on 10 September, 202023 February, 2021