Background and aims: Epidemiological and serological evidence suggest EBV infection is associated with MS pathogenesis. Previously, we showed that treatment with an autologous EBV-targeted T-cell immunotherapy in 10 patients with progressive MS may prevent MS progression and improve clinical symptoms. This study evaluates safety and feasibility of monotherapy with pre-manufactured, unrelated donor (off-the-shelf, allogeneic) EBV-targeted T-cells (ATA188) for adults with progressive MS. Methods: A phase 1 multicentre, open-label, single-arm, 2-population, dose-escalation study enrolled EBVseropositive adults with primary/secondary progressive MS (NCT03283826). Cohorts 1-4 receive 5.0x106, 1.0x107, 2.0x107, and 4.0x107 cells, respectively, on days 1, 8, and 15 in 2 cycles. Plasma inflammatory biomarkers (IL-2, IL-1β, TNF-α, IL-6) are monitored throughout treatment. Results: By 7 January 2019, 6 participants in cohort 1 (mean age: 58.2 years; 50% female) and 6 participants in cohort 2 (mean age: 56.7 years; 83% female) have received ≥1 dose. No dose-limiting toxicities or serious or grade ≥3 treatment-emergent adverse events (TEAEs) were reported. TEAEs occurred in 58% (7/12) participants (4/6 in cohort 1 and 3/6 in cohort 2); all TEAEs were grade 1 (17%) or grade 2 (42%). Most common TEAEs (n=2) were rhinorrhoea, fall, contusion, and headache. Two participants reported possibly-related grade 2 TEAEs. In cohort 1, 3 participants experienced upper respiratory infection symptoms, with 2 developing symptoms 2-5 months after treatment. Inflammatory cytokines remained at or near baseline throughout treatment. Conclusion: Initial safety data indicate ATA188 is well tolerated by adults with progressive MS and support proceeding with the study and identification of recommended phase 2 dose. Disclosure: This study was supported by Atara Biotherapeutics