TOPLINE: 

CD19 chimeric antigen receptor (CAR) T-cell therapy showed potential in treating patients with refractory systemic lupus erythematosus (SLE), with B-cell depletion and disease activity reduction observed.

METHODOLOGY:

• HN2301 is an engineered CD8 T-cell-targeted lipid nanoparticle encapsulating CD19 CAR messenger RNA (mRNA) for in vivo application. In preclinical studies in nonhuman primates, successful transfection and B-cell depletion without obvious toxic effects were noted.
• This study assessed the feasibility of in vivo CD19 CAR T-cell therapy in five patients with SLE refractory to multiple conventional therapies.
• Two patients received 2-mg and three patients received 4-mg (single or multiple) doses of HN2301. Immunosuppressive drugs were discontinued 1 week prior to the first infusion of HN2301.

TAKEAWAY:

• CD8+ CD19 CAR T cells were detectable in the peripheral blood 6 hours post-infusion; the CD19 CAR T-cell and CAR mRNA levels peaked at 6 hours after each infusion, returning to baseline within 2-3 days. Off-target expression of CAR on non-CD8+ T cells was below 10%.
• Circulating B cells were substantially reduced within 6 hours after the first treatment in patients receiving the 2-mg dose and were depleted completely in those receiving the 4-mg dose, with depletion maintained until 7-10 days after administration.
• No cases of higher-grade cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome were observed.
• Systemic Lupus Erythematosus Disease Activity Index 2000 scores decreased in all patients at 3 months after the HN2301 treatment.

IN PRACTICE:

“These data support the potential role of in vivo CAR T-cell therapy in autoimmune disease,” the researchers wrote. “More data are necessary to determine the durability of effect and the appropriate dose and treatment schedule to achieve the immune reset necessary for long-term drug-free remission,” they added.

SOURCE:

The study was led by Qian Wang, MD, First Affiliated Hospital of University of Science and Technology of China in Hefei, China. It was reported online on September 17, 2025, in a letter to the editor published in The New England Journal of Medicine.

LIMITATIONS: 

No limitations were discussed in the correspondence.

DISCLOSURES:

The study was supported by grants from the National Natural Science Foundation of China, Anhui Provincial Natural Science Foundation, Anhui Provincial Health Research Foundation, and others to various authors. One author reported serving as a consultant for several pharmaceutical companies. Two authors reported employment with Shenzhen MagicRNA Biotech, and one author reported employment with MagicRNA.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.