CAR-NK Therapy for Systemic Lupus Erythematosus Published in The Lancet

Background

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which the immune system attacks the body’s own tissues, causing inflammation that can damage multiple organs including the skin, joints, kidneys and heart. It disproportionately affects women of reproductive age. Although standard treatments with glucocorticoids, immunosuppressants and biologic agents control disease in many cases, refractory SLE remains a significant clinical challenge, with patients experiencing persistent moderate-to-severe activity, organ damage and diminished quality of life.

Cellular therapies such as autologous CD19 CAR-T cells have recently shown potential to induce prolonged remission by depleting autoreactive B cells. However, these personalised treatments have limitations including lengthy manufacturing, high costs, infection risks and variable safety profiles. Allogeneic approaches using cells from healthy donors offer the possibility of readily available, standardised 'off-the-shelf' products.

What was achieved

Researchers at Changhai Hospital’s Department of Rheumatology and Immunology, led by Dongbao Zhao and Jie Gao in collaboration with others including Mengtao Li, conducted the first-in-human study of allogeneic CD19 CAR-NK cell therapy for relapsed or refractory SLE. The prospective case series, registered as NCT06010472, enrolled 18 patients (17 female) with moderate-to-severe disease between 21 August 2023 and 16 June 2024. Median age was 37.5 years and median disease duration 10.5 years. Patients received conditioning with fludarabine and cyclophosphamide followed by infusions of the allogeneic CAR-NK product known as KN5501.

Results published in The Lancet (online November 2025, Volume 406, Issue 10522, pages 2968-2979) showed favourable safety with only one case of grade 1 cytokine release syndrome (transient fever) and no neurotoxicity, dose-limiting toxicities or other severe adverse events. Among nine patients with more than 12 months’ follow-up (median follow-up overall over 9 months, maximum 18 months), six (67%) attained DORIS remission and lupus low disease activity state with no reported relapses. Biomarker analyses showed deep B-cell depletion in most patients followed by naive B-cell reconstitution. On 14 November 2025, the hospital established a Cell Therapy Center.

How it works

In SLE, pathogenic B cells produce autoantibodies that drive tissue damage. The therapy utilises natural killer (NK) cells harvested from healthy donors. These cells are genetically modified to express a chimeric antigen receptor (CAR) directed against CD19, a surface marker on B cells, creating the product known as KN5501. As an allogeneic therapy, it allows for large-scale batch production rather than individualised manufacturing.

Following lymphodepleting chemotherapy, patients receive the CAR-NK cell infusions. The engineered NK cells target and eliminate CD19-expressing B cells, resulting in deep B-cell depletion. Study analyses indicated subsequent reconstitution of the B-cell population with naive cells, associated with re-establishment of immune tolerance and clinical improvement. NK cells were selected in part for their lower cytokine production compared with T cells, contributing to the observed safety profile.

What it means for international patients

The study suggests allogeneic CAR-NK therapy could offer a scalable option for certain patients with refractory autoimmune diseases, addressing some limitations of autologous CAR-T approaches such as manufacturing time and certain safety considerations. Changhai Hospital’s new Cell Therapy Center integrates resources from rheumatology, haematology and other departments to advance research and application of cellular therapies for autoimmune diseases and other conditions.

The hospital accommodates international patients, who can register using passports and may access interpreter support through hospital channels or medical facilitators. Patients interested in this CAR-NK approach for SLE should contact the hospital directly to confirm current eligibility, availability, trial status or treatment protocols, as the published results describe a specific clinical case series with ongoing follow-up. Individual medical assessment by the treating physicians is required.

About the hospital

Changhai Hospital, officially the First Affiliated Hospital of Naval Medical University (also known as the First Affiliated Hospital of the Naval Medical University of the Chinese People’s Liberation Army), is a Grade 3A comprehensive teaching hospital located at 168 Changhai Road in Shanghai’s Yangpu District. Founded in 1949, it features more than 2,100 beds and handles millions of outpatient and emergency visits annually. It combines clinical care, medical education and scientific research.

The hospital maintains strengths in burn and trauma care, digestive system diseases with advanced endoscopy, urology, cardiovascular conditions and integrated traditional Chinese and Western medicine approaches to tumours. It hosts the National Key Laboratory of Immunity and Inflammation, which supported the CAR-NK research, and has now opened a dedicated Cell Therapy Center. It provides services for international patients including passport-based registration.