In-Vivo CAR T Therapy for Lupus Data from MagicRNA Published in New England Journal of Medicine in 2025
In a significant breakthrough, MagicRNA, a clinical-stage biotechnology company, has published the world's first clinical data of an mRNA-lipid nanoparticle (mRNA-LNP) based in vivo CAR T-cell therapy candidate, HN2301, in The New England Journal of Medicine. The study, led by Prof. Georg Schett, a pioneer in the use of CD19 CAR T cell therapy in SLE, represents the first-ever demonstration of in vivo CAR T generation and activity in SLE patients.
The clinical trial enrolled five patients with long-standing, treatment-refractory SLE, four of whom also had lupus nephritis. HN2301 was administered intravenously without prior lymphodepletion to deliver CAR-encoding mRNA to CD8+ T cells. The treatment was generally well tolerated, with no patients experiencing grade ≥3 CRS, and no neurotoxic effects or other severe adverse events observed during or after treatment.
The study showed that HN2301 reprogrammed the CD8+ T cells into CD19-targeted CAR T cells in vivo. At a minimal dose (2 mg per infusion), single or repeated administration of HN2301 induced CAR T-cells generation and B-cell reduction. Complete depletion of circulating B cells, which persisted for 7-10 days, was achieved with the use of HN2301.
The generated CAR T cells achieved rapid B-cell clearance. Anti-nucleosome and anti-dsDNA antibodies significantly decreased, and low complement levels in some patients normalized at the last visit. Disease Activity Index (SLEDAI-2000) scores significantly decreased by as much as 20 points in all 5 patients 3 months after the infusion of HN2301.
In vivo CAR T technology offers a new level of disease control that potentially goes beyond what has been achieved with conventional approaches such as monoclonal antibodies and T-cell engagers, while overcoming the major limitations of ex vivo CAR T therapies. At a bit higher dose (4 mg per infusion), up to 60% of CD8 CART-cells were reprogrammed within six hours.
Dr. Gavin Zha, CEO of MagicRNA, stated that the study provides the first clinical proof-of-concept of the cell targeted-LNP based in vivo CAR T-cell in autoimmune disease. The findings of the study, along with the favorable safety profile, pave the way for a new era of immunotherapy. MagicRNA aims to accelerate clinical development and ultimately bring this therapy to patients worldwide.
The company behind this groundbreaking research is Abogen Biosciences, a clinical-stage biotechnology firm specializing in in vivo CAR T-cell therapies. The study, titled 'In vivo CD19-CAR T-Cell Therapy for Refractory Systemic Lupus Erythematosus', marks a significant step forward in the treatment of refractory SLE, offering hope for patients who have not responded to conventional therapies.
