CAR Treg cells show initial efficacy in hard-to-treat rheumatoid arthritis

SBT777101 is an autologous chimeric antigen receptor (CAR) regulatory T-cell (Treg) therapy specific for citrullinated proteins, designed to restore immunological tolerance in inflammatory diseases without exerting cytotoxic effects. Preliminary data with SBT777101 showed no dose-limiting toxicities and early signs of efficacy in participants with highly refractory rheumatoid arthritis.

Dr Minna Kohler (Massachusetts General Hospital, MA, USA) presented the findings from the ongoing Regulate-RA (NCT06201416), a first-in-humans, phase 1, open-label, dose-escalation trial of SBT777101 [1]. Participants were eligible if they had met the 2010 ACR/EULAR criteria for rheumatoid arthritis, had a Disease Activity Score 28 with C-reactive protein (DAS-28-CRP) >3.2, and had failed ≥3 disease-modifying antirheumatic drugs (DMARDs) with different mechanisms-of-action. Three participants were treated per dose level, with sequential dose escalation across 3 planned dose cohorts. The primary outcome was safety and tolerability, with efficacy assessed as an exploratory endpoint. The first 2 dose levels completed dose-limiting toxicity evaluation, and data were presented for 6 participants in total.

The most common adverse events were nausea, vomiting, and headache, occurring primarily in the first week after infusion. No cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or dose-limiting toxicities were observed. Overall, 4 of 6 participants achieved ≥50% reduction in swollen or tender joint counts at week 4 after infusion, with deeper and more durable responses in cohort 2 (the higher-dose group) from week 4 through week 24. In 1 responding participant, CAR Treg cells were detectable in a post-treatment synovial biopsy, providing preliminary evidence of target-tissue homing and persistence of the regulatory T-cell phenotype.

“In summary, Regulate-RA is an ongoing, dose-escalation phase 1 trial of SBT777101 autologous CAR Treg cells in participants with highly refractory rheumatoid arthritis,” concluded Dr Kohler. “Interim safety and tolerability are favourable with no dose-limiting toxicities, and preliminary data indicate clinical signals of efficacy. Enrolment in cohort 3 is ongoing.”

1. Kohler M, et al. A phase 1 study of autologous CAR-Treg cells in refractory rheumatoid arthritis: Interim report of safety and efficacy. ACR Convergence, 24–29 October 2025, Chicago, IL, USA.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 30 October 202530 October 2025