What is CAR-T?
In classic autologous CAR-T, the patient’s T cells are collected, genetically modified in the laboratory to express a chimeric antigen receptor that recognizes a specific target, expanded, and infused back into the patient after lymphodepletion. One of the most studied targets in autoimmune diseases is CD19, which is found on B cells.
Why might targeting B cells work?
In lupus and certain systemic autoimmune diseases, B-cell clones that produce autoantibodies or sustain the autoimmune response play a role. Antibodies such as rituximab can deplete B cells; CAR-T, however, can achieve a much deeper and temporary elimination of CD19-bearing B cells. The hypothesis being investigated is that when B cells regenerate, the immune repertoire “restarts” in a more tolerant state.
NEJM 2024 series
In the human series published in the NEJM, 15 patients with severe autoimmune disease were evaluated: 8 with systemic lupus erythematosus, 3 with idiopathic inflammatory myositis, and 4 with systemic sclerosis. After a single CD19 CAR-T infusion, all lupus patients met the DORIS remission criteria; a major clinical response was observed in all myositis patients, and disease activity decreased in the systemic sclerosis group. Immunosuppressive therapy could be discontinued in all patients. Median follow-up was 15 months.
Why are these results noteworthy?
The most striking observation is that disease remission persists in some patients even after B cells return. This supports the concept that the immune repertoire can be reorganized, distinct from mere temporary immunosuppression alone. However, an uncontrolled series of 15 patients is not definitive proof of efficacy.
2025: the in-vivo CAR-T concept
In early human data reported in the NEJM in 2025, generating CAR-T cells inside the body using lipid nanoparticles was reported to result in B-cell depletion and a reduction in disease activity in refractory lupus patients. This approach has the potential to reduce costly and complex ex-vivo cell manufacturing in the future; it is still in the early research stage.
2026: SPS and myasthenia gravis
In 2026, long-term positive signals were announced for mivocabtagene autoleucel (miv-cel/KYV-101) in stiff person syndrome and generalized myasthenia gravis cohorts. However, a significant portion of these results comes from the company’s topline clinical data release; randomized and fully peer-reviewed results will be critical to establishing its clinical place.
Risks
- Cytokine release syndrome (CRS)
- ICANS neurotoxicity
- Prolonged cytopenia and risk of infection
- Hypogammaglobulinemia and requirement for immunoglobulin replacement
- Toxicities of lymphodepleting chemotherapy
- Rare but serious late complications
Who is it being investigated for?
Current studies generally include selected patients whose severe disease persists despite standard immunosuppressive and biological therapies, and who are at high risk for organ damage. In mild autoimmune disease, the benefit-risk balance is entirely different.
CAR-T and stem cell therapy are not the same thing
No. CAR-T is a targeted immune cell therapy performed with genetically reprogrammed T lymphocytes. It is completely different from mesenchymal stromal cell, SVF, or regenerative orthopedic cell applications in terms of biology, purpose, manufacturing, and risks.
Related reading
Miv-cel 12-Month New Clinical Data · Cell Therapies · Stem Cell Therapies and Clinical Evidence
References
- Müller F, et al. CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up. N Engl J Med. 2024;390:687-700. DOI: 10.1056/NEJMoa2308917.
- Wang Q, et al. In Vivo CD19 CAR T-Cell Therapy for Refractory Systemic Lupus Erythematosus. N Engl J Med. 2025;393:1542-1544. DOI: 10.1056/NEJMc2509522.
- Kyverna Therapeutics. Miv-cel SPS/gMG 12-month topline clinical data, September 24, 2026.
Last medical review: September 25, 2026
