MagicRNA, a clinical-stage biotech pioneering in vivo CAR T-cell therapies, announced the publication of the world’s first clinical data of an mRNA-LNP-based in vivo CAR T candidate, HN2301, in The New England Journal of Medicine.
The study, titled In vivo CD19-CAR T-Cell Therapy for Refractory Systemic Lupus Erythematosus, marks the first-ever demonstration of in vivo CAR T generation and activity in SLE patients.
A Breakthrough for Immunotherapy
“This study is an important milestone for the entire field of cell therapy,” said Prof. Georg Schett, a pioneer in CD19 CAR T therapy for SLE.
“For the first time, we see functional CAR T cells generated directly in patients, achieving rapid B-cell clearance and clinical improvement.”
The trial enrolled five patients with long-standing, treatment-refractory SLE. Four also had lupus nephritis.
HN2301, built on MagicRNA’s EnC-LNP delivery platform, was administered intravenously without lymphodepletion. The therapy delivered CAR-encoding mRNA to CD8+ T cells, reprogramming them into CD19-targeted CAR T cells in vivo.
Clinical Results
At 2 mg per infusion, single or repeated administration induced CAR T generation and B-cell reduction.
At 4 mg per infusion, up to 60% of CD8+ CAR+ T cells were reprogrammed within six hours, causing complete B-cell depletion for 7–10 days.
Consistent with this effect:
- Anti-nucleosome and anti-dsDNA antibodies decreased.
- Complement levels normalized in some patients.
- SLEDAI-2000 scores dropped by as much as 20 points in all patients within three months.
Safety Profile
Treatment was well tolerated.
- No grade ≥3 cytokine release syndrome (CRS).
- No neurotoxic effects.
- No severe adverse events.
- No clinically significant liver enzyme elevations
Expert Commentary
“This study validates the therapeutic potential of in vivo CAR T in autoimmune disease,” said Dr. Gavin Zha, CEO of MagicRNA.
“By achieving deep B-cell depletion, we can go beyond monoclonal antibodies or T-cell engagers. At the same time, we overcome the major limitations of ex vivo CAR T—complex manufacturing, long preparation, high costs, and lymphodepletion.”
Next Steps
Based on these findings, MagicRNA will continue dose-escalation studies to explore immune reset and long-term drug-free remission.
The company aims to accelerate clinical development and bring this therapy to patients worldwide.
About HN2301
- First in vivo CAR T candidate to enter clinical testing in SLE patients.
- Encapsulates CD19 CAR mRNA in a proprietary T-cell-targeted lipid nanoparticle (EnC-LNP).
- Enables direct reprogramming of T cells into functional CAR T cells.
- Preclinical studies in mice and nonhuman primates showed robust CAR T generation and B-cell depletion.
- Early human data confirm feasibility, efficacy, and safety.
About MagicRNA
Founded in 2021, MagicRNA is a clinical-stage biotech advancing next-generation mRNA and LNP technologies.
The proprietary EnC-LNP platform delivers mRNA into non-APCs outside the liver, overcoming limitations of conventional LNPs.
Pipeline:
- HN2301 (lead program in SLE).
- Other in vivo cell reprogramming therapies and cell-targeted LNP medicines in immune-related diseases.
About SLE
Systemic Lupus Erythematosus (SLE) affects 3.4 million people globally (44 per 100,000 prevalence).
It disproportionately impacts women of childbearing age, causing immune-driven inflammation and multi-organ damage. Lupus nephritis is the most severe form.
Standard treatments—corticosteroids, immunosuppressants, biologics—can control symptoms but often fail to prevent relapses and progressive organ damage.
B cells play a pivotal role by producing autoantibodies. Resetting B cells has been linked to durable, drug-free remission.
HN2301 offers the first clinical proof-of-concept that in vivo CAR T therapy can deliver this reset safely and effectively.
