Scientists at the First Affiliated Hospital of the University of Science and Technology of China report that an in‑body CD8 T‑cell‑targeted lipid nanoparticle delivering CD19 CAR mRNA (HN2301) produced short‑lived CAR T cells that quickly removed B cells and lowered disease activity in five patients with medication‑resistant systemic lupus erythematosus.
Lupus is a long‑term autoimmune condition in which the immune system creates antibodies that attack the body’s own tissues, causing inflammation and damage to organs such as the kidneys, joints, skin, and nervous system. Existing therapies—mainly corticosteroids and immunosuppressants—aim to reduce inflammation, yet patients often experience relapses and resistance, underscoring a need for treatments that can sustain remission.
Autologous CD19 CAR T‑cell therapy has shown promise in autoimmune diseases, but high cost and the need for conditioning chemotherapy limit its widespread adoption. Strategies that generate CAR T cells directly in the body using lipid nanoparticles or lentiviral vectors have been described previously, yet their clinical efficacy and safety in autoimmune disease remain unclear.
In a letter to the editor titled “In Vivo CD19 CAR T-Cell Therapy for Refractory Systemic Lupus Erythematosus,” published in The New England Journal of Medicine as a Correspondence, researchers share the outcomes of a feasibility study in five lupus patients.
All five participants had previously failed multiple standard therapies; every patient except Patient 4 also had lupus nephritis. HN2301 was given on a three‑dose exploratory schedule: 2 mg for Patients 1 and 2, and 4 mg for Patients 3, 4, and 5.
CD8⁺ CD19 CAR T cells could be detected in peripheral blood within six hours of infusion. CAR T‑cell and mRNA levels peaked at six hours after each dose and returned to baseline within two to three days. Off‑target CAR expression on non‑CD8⁺ T cells was below 10 %. CD69 up‑regulation appeared on CD8⁺ T cells but not on CD4⁺ T cells.
Within six hours after the first treatment, circulating B cells fell sharply at the 2 mg dose and were virtually wiped out—fewer than one B cell per microliter—at the 4 mg dose, with depletion lasting seven to ten days.
No severe cytokine release syndrome (grade 3/4) or immune‑effector‑cell‑associated neurotoxicity occurred. Elevated C‑reactive protein and interleukin‑6 were observed, and three patients received a single dose of tocilizumab for cytokine release management.
Liver enzymes remained normal, and no cytopenia beyond a transient lymphocyte drop was reported. In Patients 4 and 5, anti‑nucleosome and anti‑double‑stranded DNA antibodies decreased markedly, with low complement levels returning to normal.
Three months after HN2301 administration, systemic lupus erythematosus disease activity scores (SLEDAI‑2000) declined in all five patients. Although the data are limited, they suggest early evidence of an immune reset.
The authors conclude that in‑vivo CAR T‑cell therapy can generate functional CD19 CAR T cells in lupus patients that deplete B cells and modulate disease‑related autoantibodies and clinical activity. Additional data and longer follow‑up are necessary to determine the durability of this preliminary signal.