Xu Huji Team Uses Universal STAR-T Cell Therapy to Successfully Treat Systemic Lupus Erythematosus

Background

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which the immune system attacks the body's own tissues and organs. It can lead to serious complications such as lupus nephritis, which affects the kidneys. For patients with refractory disease that does not respond to standard immunosuppressive treatments, options have been limited, often resulting in ongoing organ damage and reduced quality of life.

A team led by Professor Huji Xu from the Department of Rheumatology and Immunology at Shanghai Changzheng Hospital collaborated with researchers from Tsinghua University to explore advanced cell therapies. Their work on a universal STAR-T cell product, known as YTS109, represents an early clinical application in this field. The findings from a phase 1 trial were published in the journal Nature Medicine.

What was achieved

In an investigator-initiated trial (NCT06379646), five patients with severe, treatment-refractory SLE complicated by lupus nephritis (ISN/RPS class III+V or IV+V) were enrolled between April and July 2024. The patients, four women and one man aged 23 to 41 years with disease durations of 3 to 30 years, received lymphodepletion chemotherapy followed by a single infusion of YTS109 at a dose of 3 × 10^6 STAR-positive T cells per kilogram of body weight.

All five patients achieved a SLE Responder Index 4 (SRI-4) response by month 3, which was sustained through month 6. Four patients experienced a rapid and sustained reduction in SELENA-SLEDAI disease activity scores from a mean of 31.30 to 5.35 by month 6, with complete resolution of symptoms including proteinuria, arthritis, alopecia, vasculitis and rash in several cases. Quality of life measures improved across all patients. Renal biopsies in some cases confirmed resolution of inflammation and tissue restoration. The therapy was well tolerated, with only mild cytokine release syndrome observed and no cases of graft-versus-host disease. The results were published on August 27, 2025.

How it works

STAR-T cell therapy uses T cells from healthy donors rather than the patient's own cells, making it a universal or off-the-shelf approach. The cells are genetically engineered using CRISPR-Cas9 technology. Specific genes (TRAC, PD1, HLA-A, HLA-B and CIITA) are knocked out to reduce the risk of immune rejection and improve persistence. A synthetic T cell receptor and antigen receptor (STAR) targeting the CD19 protein is precisely inserted into the TRAC locus. This design aims to provide signaling more similar to natural T cell receptors compared to traditional CAR constructs.

CD19 is a marker found on B cells, which in SLE produce harmful autoantibodies that drive the disease. The infused STAR-T cells target and deplete these B cells. Prior to infusion, patients undergo lymphodepletion to temporarily reduce their existing lymphocytes, creating space for the new cells to expand and function. This process is intended to reset the immune system, reducing autoimmune activity and allowing tissue repair, as observed in the kidney biopsies.

What it means for international patients

This early trial suggests that universal STAR-T therapy may offer a new avenue for patients with hard-to-treat SLE and lupus nephritis, potentially leading to rapid clinical responses and reduced reliance on long-term immunosuppression. Shanghai Changzheng Hospital maintains special needs or VIP services that support international patients, including those from abroad who register with passports. The hospital has experience managing complex autoimmune and rheumatic conditions through its rheumatology and immunology department.

International patients interested in this or similar therapies should confirm current availability, eligibility criteria and regulatory status directly with the hospital, as this remains an investigational treatment from a phase 1 study. Suitability depends on individual medical profiles and ongoing research protocols.

About the hospital

Shanghai Changzheng Hospital, formally the Second Affiliated Hospital of Naval Medical University, is a Grade IIIA tertiary comprehensive hospital located at 415 Fengyang Road in Shanghai's Huangpu District. Established in 1900 as Baolong Hospital by a German physician, it has grown into a major center for medical care, education and research under the administration of the People's Liberation Army Navy.

The hospital is recognized for its strengths in orthopedics and spine surgery, neurosurgery, nephrology and rheumatology and immunology. It was ranked among the top 100 hospitals in the 2023 China Hospital Comprehensive Ranking. It provides services for international and VIP patients, with support for foreign nationals including appointment coordination.