Chinese biotechnology company MagicRNA has published the world's first clinical data on its in vivo CAR T-cell therapy HN2301 for refractory systemic lupus erythematosus (SLE) in the New England Journal of Medicine. The study shows that HN2301, an mRNA lipid nanoparticle (mRNA-LNP), reprograms up to 60% of CD8+ T cells into CAR T cells, leading to complete depletion of circulating B cells and a reduction in SLEDAI score by up to 20 points within three months.
The study included five patients with long-standing, treatment-resistant SLE, four of whom had lupus nephritis. HN2301, based on MagicRNA's EnC-LNP platform, was administered intravenously without prior lymphodepletion. At a dose of 4 mg per infusion, up to 60% of CD8+ T cells were reprogrammed into CD19-directed CAR T cells within six hours, resulting in sustained B-cell depletion for 7–10 days. Anti-nucleosome and anti-dsDNA antibodies decreased significantly, and low complement levels normalized in some patients. The therapy showed a favorable safety profile with no neurotoxic effects, severe adverse events, or clinically relevant elevations in liver enzymes.
"This data marks a milestone for cell therapy," said Prof. Georg Schett, a pioneer in CD19 CAR T-cell therapy for SLE. "Generating functional CAR T cells directly within patients' bodies opens up new avenues for immunotherapy." Dr. Gavin Zha, CEO of MagicRNA, emphasized that the technology overcomes the complex manufacturing, long lead times, and high costs of ex vivo CAR T-cell therapies, making transformative treatments scalable.
MagicRNA plans further dose-escalation studies to investigate HN2301's ability to achieve a "B-cell reset" and long-term remission. SLE affects approximately 3.4 million people worldwide, predominantly women of childbearing age, and often leads to severe complications such as lupus nephritis. Existing treatments like corticosteroids and biologics can control symptoms, but many patients experience recurrent flares.
