CAR-T cell therapy results in sustained lupus remission

CD19-targeted chimeric antigen receptor (CAR) T-cell therapy results in sustained suppression of autoantibodies in treatment-resistant systemic lupus erythematosus (SLE), according to a study from a German group. These findings suggest that the main cellular source of autoantibodies in SLE is CD19+ plasmablasts. Vaccination responses were not affected.

CAR T-cell therapy may be an option if immunosuppressive or immunomodulatory therapies fail in SLE. This immunotherapy is successfully used to treat B-cell malignancies and multiple myeloma. A German research group led by Dr Georg Schett (University Hospital Erlangen, Germany) investigated whether CAR T-cell therapy could lead to sustained suppression of SLE-specific autoimmunity and whether it affects long-term vaccination response [1]. The investigators were encouraged by their own previous findings that CD19 CAR T-cell therapy leads to stable, drug-free remission of treatment-resistant SLE [2].

The study consisted of administering a single infusion of 1 million CD19 CAR T cells per kg body weight to 8 patients with treatment-resistant SLE between March 2021 and June 2023. Patients had stopped immunosuppressive treatment before CAR T-cell infusion. SLE disease activity was monitored between 1 and 2 years. Autoantibodies were measured at baseline, 3 months after CAR T-cell therapy, and at the last follow-up.

At the time of analysis (June 2023), 5 participants had a follow-up duration of more than 1 year after treatment with CAR T cells. All 8 patients were in remission and had a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 0. They were off any immunosuppressive medication. Autoantibodies against dsDNA (4/5), ssDNA (4/5), nucleosomes (5/5), secondary necrotic cells (4/5), and Smith antigen (3/5) disappeared. The one exception was a patient with a nucleosome antibody response.

Vaccination response against measles, mumps, rubella, varicella-zoster, Epstein-Barr, tetanus, and pneumococcus remained stable and robust after treatment. Apparently, antibodies related to vaccination responses predominantly stem from CD19-negative plasma cells, whereas the main source of autoantibodies in SLE may be CD19+ plasmablasts, which are sensitive to CD19 CAR T-cell therapy.

1. 
   
   1. Schett G, et al. CAR T-cell therapy leads to long-term abrogation of autoimmunity in SLE patients while vaccination responses are maintained. 0607, ACR Convergence 2023, 10–15 November, San Diego, USA.
   2. Mackensen A, et al. Nat Med. 2022;28(10):2124-2132.

 

Medical writing support was provided by Michiel Tent.
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Posted on 1 December 20231 December 2023