Off-the-Shelf CAR T Shows Early Signal in Progressive Multiple Sclerosis

Phase I data show B-cell depletion and mostly stable or improved disability scores, but the uncontrolled study remains small and follow-up is limited

November 2, 2026
3 min

The Medicine Maker

At a Glance

Category	Detail
Condition	Progressive multiple sclerosis (primary progressive, active secondary progressive, or non-active secondary progressive)
Key Mechanisms	Azer-cel is an investigational allogeneic CD19-directed CAR T-cell therapy intended to deplete B cells in blood, tissues, and cerebrospinal fluid.
Target Population	Adults with progressive MS and disability progression independent of relapse activity during the prior year despite high-efficacy treatment; all study participants had previously received anti-CD20 therapy.
Care Setting	Phase I clinical-trial setting; participants received bendamustine lymphodepletion followed by a single azer-cel infusion.

Key Highlights

The ongoing Phase I TG-Azercel-101 study included 26 people with progressive MS.
Peripheral B-cell counts fell below 10 cells per microliter in 25 of 26 participants.
Among 21 participants with paired cerebrospinal fluid samples, median CD19-positive B-cell events declined by 52.3% at day 10.
At day 90, disability scores were stable or improved in 16 of 18 evaluable participants; seven of eight assessed at six months remained stable or improved.
Median follow-up at the September 3 data cutoff was 4.9 months.

Guideline-Based Recommendations

Diagnosis

Management

In the study, participants received bendamustine lymphodepletion followed by one infusion of 30 million to 500 million CAR T cells.

Monitoring & Follow-up

The study assessed peripheral B-cell counts, cerebrospinal fluid CD19-positive B-cell events, and Expanded Disability Status Scale scores.

Risks

No dose-limiting toxicities, grade 3 or higher cytokine release syndrome, grade 2 or higher immune effector cell-associated neurotoxicity syndrome, graft-versus-host disease, or immune effector cell-associated hemophagocytic syndrome were reported.
Two participants experienced grade 1 or 2 cytokine release syndrome and two developed grade 1 or 2 neurotoxicity.
Eleven participants experienced grade 3 or higher treatment-emergent adverse events, and four had serious adverse events.

Patient & Prescribing Data

The 26 participants had primary progressive, active secondary progressive, or non-active secondary progressive MS, prior anti-CD20 treatment, and disability progression independent of relapse activity during the previous year despite high-efficacy therapies.

Azer-cel is made from healthy donor T cells for off-the-shelf use. The study evaluated a single infusion after bendamustine lymphodepletion; the reported results are initial findings from an ongoing Phase I study.

Clinical Best Practices

Interpret the reported disability and safety findings in the context of an ongoing Phase I study with a median follow-up of 4.9 months.
The article reports investigational study findings and does not provide clinical practice recommendations.