Background: Mounting evidence suggests Epstein-Barr virus (EBV) is a necessary risk factor for development of multiple sclerosis (MS) [Abrahamyan et al. JNNP 2020]. Early experience with autologous EBV-specific T-cell therapy proved safe and may offer clinical benefit [Pender MP et al. JCI Insight 2018; Ioannides ZA et al. Front Neurol 2021]. Objectives: Evaluate the safety and potential efficacy of ATA188 in adults with progressive MS in an ongoing open-label extension (OLE) study, including an imaging biomarker: magnetization transfer ratio (MTR). Methods: In part 1 of this 2-part Phase I/II study, 4 cohorts received escalating doses of ATA188. Patients (pts) were followed for 1 year and could participate in a 4-year OLE. Sustained disability improvement (SDI; including sustained improvement in the expanded disability status scale [EDSS] and timed 25-foot walk), as well as safety, were measured [Pender MP et al. EAN 2020]. Change from baseline in MTR, a marker of myelin density, was assessed as a potential biomarker of disability improvement (exploratory endpoint). To correct for variability related to scanner differences, MTR values were normalized (nMTR; Brown RA et al. Proc Intl Soc Mag Reson Med 2011). Results: 25 pts received ⩾1 dose of ATA188 and were followed for up to 39 mos (m). No grade >3 adverse events (AE), dose-limiting toxicities, cytokine release syndrome or graft vs host disease were observed. 2 treatment-emergent serious AEs were previously reported (muscle spasticity [grade 2; not treatment related]; MS relapse [grade 3; possibly treatment related]) and, as of August 2021,1 was reported in the OLE (fall; grade 2; not treatment related). Efficacy was evaluated in 24 pts in the initial 12m period and, as of August 2021, in 18 pts in the OLE followed for up to 39m. 9 pts met SDI criteria either in the initial 12m period (n=7) or in the OLE (n=2); of these, 7 had sustained EDSS improvement. Of the 8 pts who achieved SDI participating in the OLE, 7 maintained SDI at all subsequent timepoints. The median time over which SDI was sustained in these 8 patients was 18 (range 0.03-27.0) months. Pts with sustained EDSS improvement (vs those without) at any point in the study had significantly greater increases in nMTR signal in unenhancing T2 lesions at 12m versus baseline. In general, there was a trend for an association between increase in nMTR and improvement in EDSS scores. Conclusions: Preliminary data indicate ATA188 is safe and well tolerated. Sustained EDSS improvement drove SDI in most pts, and in all but 1 pt, once SDI was achieved, it was maintained at all subsequent timepoints. Pts with sustained EDSS improvement (vs those without) showed greater increases in nMTR at 12m, providing evidence that structural changes suggestive of remyelination are associated with prolonged sustained improvement. The Phase 2 portion of this study, EMBOLD (NCT03283826), is ongoing and currently enrolling.