MagicRNA In Vivo CAR T Lupus Data 2025 Hits New England Journal of Medicine

SHENZHEN, China, Sept. 18, 2025 /PRNewswire/ -- MagicRNA, a clinical-stage biotechnology company pioneering in vivo CAR T-cell therapies, today announced the publication of the world's first clinical data of an mRNA-lipid nanoparticle (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", represents the first-ever demonstration of in vivo CAR T generation and activity in SLE patients.

"This study is an important milestone for the entire field of cell therapy," said Prof. Georg Schett, pioneer in the use of CD19 CAR T cell therapy in SLE and achieved a revolutionary breakthrough. "For the first time, we see functional CAR T cells generated directly in patients' body, achieving rapid B-cell clearance and clinical improvement of autoimmune disease. These findings, together with the favorable safety profile, pave the way for a new era of immunotherapy."

The clinical trial enrolled five patients with long-standing, treatment-refractory SLE, four of whom also had lupus nephritis. Built on MagicRNA's EnC-LNP delivery platform technology, HN2301 was administered intravenously without prior lymphodepletion to deliver CAR-encoding mRNA to CD8+ T cells, reprogramming them into CD19-targeted CAR T cells in vivo.

"This study marks the first clinical proof-of-concept of the cell targeted-LNP based in vivo CAR T-cell in autoimmune disease, validating its therapeutic potential in patients," said Dr. Gavin Zha, CEO of MagicRNA. "By achieving deep B-cell depletion, 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. At the same time, it overcomes the major limitations of ex vivo CAR T therapies, including complex manufacturing, long preparation times, high costs, and the requirement for lymphodepletion. Our platform has the potential to make transformative cell therapies broadly accessible and scalable for patients."

At a minimal dose (2 mg per infusion), single or repeated administration of HN2301 induced CAR T-cells generation and B-cell reduction. At a bit higher dose (4 mg per infusion) up to 60% of CD8⁺ CAR⁺T-cells were reprogrammed within six hours, leading to complete depletion of circulating B cells, which persisted for 7-10 days. Consistent with B-cell depletion, anti-nucleosome and anti-dsDNA antibodies significantly decreased, and low complement levels in some patients normalized at the last visit. In addition, 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. The treatment was generally well tolerated, no patients experienced grade ≥3 CRS, and no neurotoxic effects or other severe adverse events were observed during or after treatment.

Based on these encouraging clinical results, MagicRNA will continue the dose-escalation studies to further evaluate HN2301's ability to achieve immune reset and long-term drug-free remission, with the goal of accelerating clinical development and ultimately bringing this therapy to patients worldwide.