CAR T Cells Highly Effective for Autoimmune Disorders


CD19-directed CAR-T-cell therapy resulted in sustained remission for over a year and no return of autoimmunity for patients with systemic lupus erythematosus, idiopathic inflammatory myositis, and systemic sclerosis.

Fabian Müller, MD, of Bavarian Cancer Research Institute and Friedrich-Alexander University of Erlangen-Nuremberg

Fabian Müller, MD

All patients treated with a CD19-directed chimeric antigen receptor (CAR)-modified T-cell therapy remained in remission with more than a year of follow up for patients with heavily pretreated systemic autoimmune diseases with multiple organ involvement, according to findings from the 2023 ASH Annual Meeting.

In the single institution study, MB-CART19.1 was administered to patients with systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc). In addition to sustained remissions, the CAR T-cell therapy was well tolerated, with limited adverse events (AEs) commonly associated with CAR T-cell therapies. Additionally, patients saw a reconstitution in their B cell counts, without a return in autoimmunity, with all patients able to remain off disease-specific treatment since receiving the CAR T cell infusion.

“Disease-specific treatment was stopped, and symptom control was achieved in all patients treated up to date,” said lead investigator Fabian Müller, MD, of Bavarian Cancer Research Institute and Friedrich-Alexander University of Erlangen-Nuremberg. “B cells and disease-defining autoantibodies are quickly abrogated. Naive B cells remain the dominant phenotype up to 12 months after CART.”

The study included 15 patients, which consisted of 8 with SLE, 4 with SSc, and 3 with IIM. The median age of patients was 36 years, and the median duration of disease was 4 years (range, 1-20). For all patients, autoantibodies were present at baseline, and all had at least 2 organs involved, including the skin (n = 13), lung (n = 11), kidney (n = 9), joints (n = 9), heart (n = 4), muscles (n = 3), and others. The median number of prior therapies was 5 (range, 2-14) and all prior therapies were stopped before the study, except for up to 10 mg of daily prednisolone.

MB-CART19.1 is produced using the Miltenyi closed and fully automated prodigy platform, Müller noted. This took approximately 2 weeks to manufacture within the clinic following leukapheresis during which time patients underwent lymphodepletion using intravenous fludarabine 25 mg/m2 per day on days -5 to -3 and IV cyclophosphamide 1000 mg/m2 on day -3. MB-CART19.1 was administered at 1 x 106 CAR+ T cells per kilogram of body weight.

The CAR T cells demonstrated rapid expansion following infusion with a peak at 9 days and CD19-positive B cells eliminated after a mean of 5.9 days. This is comparable to malignant diseases, Müller said. Interestingly, the B cells re-occurred in 12 of 15 patients, with the remaining having B cell aplasia. For those whose B cells returned, they did not show signs of autoimmunity, Müller noted. “The long-lived plasma cells remain fully functional, we have only naive B cells that are coming back, so it's an entire reset of the B cells,” he said.

For the ASH presentation, the median follow up was 15 months, with all patients remaining in remission. Those with SLE experienced a rapid drop in disease activity, with all having a SLE Disease Activity Index (SLEDAI) of 0 since the 6 month, with none currently receiving any disease-specific therapy since the CAR T cells.

For those with IIM, the creatinine kinase levels and muscle strength both normalized rapidly follow treatment with the CAR T cells. All patients remained in remission at the data cutoff and were not on disease-specific therapy. For those with SSc, there was a reduction in skin stiffness and vasculitis and a reversal of lung fibrosis. Additionally, there were no flairs or the need for additional autoimmune therapies.

“The very first patient worldwide that had been treated for her lupus was at a spot where she didn't have any other treatment, and her life expectancy was rather short at that time, and she said she doesn't want to live like that, she needs her treatment,” recounted Müller. “And that's a sentence that we have heard a couple of times from many different patients, and you see that all of them are doing well.”

The AE profile was relatively mild for the CAR T cell therapy. There were some low-grade inflammatory events with grade 0 (n = 4), 1 (n = 10), and 2 (n = 1) cytokine release syndrome (CRS). There was 1 case of potential immune-effector cell associated neurotoxicity syndrome with the treatment, which presented as vertigo. Of those treated, 6 received tocilizumab to manage these AEs. There were few patients with hypogammaglobulinemia.

Infections were the most common AE, with 14 of the 15 patients having either a respiratory or urinary tract infection, which is common with autoimmune disorders, Müller said. There were 3 cases of serious infectious complications, with 1 patient requiring hospitalization due to pneumonia and 2 having reactivation of herpes zoster approximately 6 to 12 months after CAR T.

“When we treat patients with the CD19 CARs in hematology, we see that these CAR T cells have substantial inflammation, which we don't see to that extent in the autoimmune patients,” said Müller. “We only saw very low grade of inflammatory side effects.”

This study was a joint endeavor between the rheumatology and hematology/oncology departments. Other studies are assessing CAR T-cell therapies for autoimmune diseases, with a distinct focus on SLE. The ASH researchers noted that an investigator-initiated study of MB-CART19.1 remains under way.

“Those diseases that respond to CD20 antibody treatment are likely to respond to the CD19 CAR-T as well,” said Müller. “There are a couple of reports coming up for neurological diseases. Multiple sclerosis is also on the table. There are no reports yet on that but there are numerous trials coming up very shortly, so it's an exciting time.”

Click here for more coverage of ASH 2023.


Müller F, Taubmann J, Voelkl S, et al. CD19-Targeted CAR-T Cells in Refractory Systemic Autoimmune Diseases: A Monocentric Experience from the First Fifteen Patients. Blood. 2023;142(suppl 1):220.doi:10.1182/blood-2023-180547.

Related Videos
Daniel Hart, PhD, on CRISPR-Mediated, In Vivo Epigenomic Activation
Luke Roberts, MBBS, PhD, on Developing Gene Therapy for Congestive Heart Failure
Sowmya Viswanathan, PhD, on Translating Cell Therapies to the Clinic at ISCT 2024
Omar Nadeem, MD, on Initial Efficacy of GPRC5D-CAR in R/R Multiple Myeloma
Omer A. Abdul Hamid, MD, on Improving Gene Therapy’s Effect and Accessibility
George Tachas, PhD, on Tackling DMD Treatment From Multiple Angles
David Suhy, PhD, the cofounder and chief scientific officer of Earli
Jeffrey Chamberlain, PhD, on Helping Progress Cell and Gene Therapy Development
Jacques Galipeau, MD, on Highlights from ISCT 2024’s Presidential Plenary
Vanee Pho, PhD, the senior director of product management, cell and gene therapy, at Mission Bio
Related Content
© 2024 MJH Life Sciences

All rights reserved.