Core Viewpoint - The article discusses the successful application of in vivo CAR-T cell therapy for treating refractory systemic lupus erythematosus (SLE), highlighting its potential to provide rapid and lasting relief without severe side effects [2][3][14]. Group 1: Research Background - In August 2021, a team from Erlangen-Nuremberg University published a paper in NEJM demonstrating the use of CAR-T cell therapy for systemic lupus erythematosus, leading to rapid and sustained relief for patients [2]. - Traditional CAR-T cell therapy is complex and costly, requiring chemotherapy pretreatment, which can cause serious side effects [2][5]. Group 2: Study Details - A paper published on September 17, 2025, in NEJM presented the first human clinical study using mRNA-LNP based in vivo CAR-T cell therapy for SLE [2]. - The study involved five patients with refractory SLE, showing B cell clearance and reduced disease activity without severe toxic effects [3][8]. Group 3: Technology and Methodology - The in vivo CAR-T cell therapy utilizes engineered lipid nanoparticles (EnC-LNP) to deliver CD19 CAR mRNA directly to CD8+ T cells, generating functional CAR-T cells in situ [5][6]. - HN2301, developed by Hongxin Biotech, successfully transduced CD19 CAR into CD8+ T cells in preclinical studies without significant toxicity [6][10]. Group 4: Treatment Outcomes - After HN2301 infusion, CD8+ CD19 CAR-T cells were detectable within 6 hours, with significant B cell reduction observed in patients receiving higher doses [10]. - No severe cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome was reported, with only mild side effects noted [12][14]. Group 5: Efficacy and Future Directions - All five patients showed a decrease in systemic lupus erythematosus disease activity index scores after three months of treatment, indicating improved disease activity [12][14]. - The findings support the feasibility and effectiveness of in vivo CAR-T cell therapy in autoimmune diseases, although further data is needed to assess long-term efficacy and appropriate dosing for sustained remission [14].