On August 27, 2025, a groundbreaking study led by BriSTAR Immunotech, in collaboration with Professor Huji Xu’s team from The Changzheng Hospital of Naval Medical University and Professor Xin Lin from Tsinghua University, was published in the top international journal Nature Medicine (Impact Factor: 58.7). This research marks the world’s first report on the efficacy and safety of YTS109—a hypoimmune allogeneic T cell product—for treating refractory systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN). Notably, among all publicly available clinical studies of its kind, this trial distinguishes itself by enrolling patients with the most severe baseline LN and the largest sample size to date, rendering its data exceptionally clinically relevant and reference-worthy.  

The publication of this study in a premier international journal not only reflects the global academic community’s strong recognition of YTS109’s clinical value but also validates the transformative potential of universal STAR-T technology in autoimmune disease research. It is poised to offer a long-awaited new treatment option for patients with hard-to-treat autoimmune conditions. (Click here to access the full study.)  

Addressing Unmet Clinical Needs in Refractory SLE/LN  

The study focuses on addressing the unmet clinical needs of patients with refractory SLE, particularly those complicated with severe LN. These patients have long faced clinical challenges, including limited efficacy with immunosuppressants, high relapse rates, and significant social burdens. While autologous CD19 CAR-T therapies have shown benefit, they are limited by personalized manufacturing, high costs, and risks from random genomic insertion.

To overcome these bottlenecks, Bristar Immunotech developed YTS109 — a hypoimmune allogeneic T cell productthat targets the CD19, aiming to provide a safe and effective new treatment regimen for patients with refractory lupus.  

Technological Advantages of YTS109  
YTS109 is built on the STAR (Synthetic T cell Receptor and Antigen Receptor) technology platform and integrated with advanced gene editing strategies:  
- BriSTAR Immunotech’s novel STAR-T technology combines the direct antigen recognition capability of chimeric antigen receptors (CARs) and the natural signal transduction function of T cell receptors (TCRs). It exhibits technical advantages such as high sensitivity, strong tissue infiltration, resistance to exhaustion, inherent dual-targeting potential, and excellent safety.  
- The further developed allogeneic STAR-T is engineered using CRISPR-Cas9 gene editing tools and adeno-associated virus (AAV)-mediated site-specific integration strategies. The STAR structure compensates for the partial functions of endogenously knocked-out TCRs, reducing the risks of graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) in universal STAR-T cells while enhancing their ability to resist immunosuppression and kill tumors.  

Preclinical studies confirmed that YTS109 possesses the following characteristics: efficient target-specific killing (especially for cells with low CD19 expression), low immunogenicity, effective reduction of NK cell-mediated killing, mitigation of host T cell responses, controllable off-target effects, and no safety risks such as chromosomal abnormalities.  

Promising Results from the Investigator-Initiated Trial (IIT)  
This investigator-initiated clinical trial (NCT06379646) enrolled 5 patients (4 females, 1 male; aged 23–41 years; disease duration 3–30 years) with severe, refractory SLE complicated with LN (International Society of Nephrology/Renal Pathology Society [ISN/RPS] Class III+V or IV+V) between April and July 2024. All patients had high baseline disease activity (SLEDAI-2K: 16–32; SLE-DAS: 15.06–42.02) and had failed multiple prior treatments, including glucocorticoids, immunosuppressants, and biological agents.  

After YTS109 infusion, all patients achieved  rapid and sustained clinical benefits, with the following encouraging outcomes:  

1. Rapid and Significant Efficacy  
- 100% achievement of SLE Response Index 4 (SRI-4): All patients rapidly met the criteria for sustained SRI-4 response by Month 1 (M1) post-infusion.  
- 4 patients had a SELENA-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score reduced to 0, with complete resolution of clinical symptoms such as proteinuria, arthritis, alopecia, vasculitis, and rash. These patients also showed a significant decrease in anti-dsDNA antibody levels and rapid recovery of complement levels.  
- 4 patients achieved Lupus Low Disease Activity State (LLDAS) remission; 2 patients achieved Definition of Remission in SLE (DORIS) remission.  
- According to LN efficacy assessment criteria: 2 patients achieved complete response (CR, 24-hour urinary protein <500 mg); 2 patients achieved partial response (PR, >50% reduction in 24-hour urinary protein). All patients remain in sustained remission to date.  

2. Favorable Safety Profile  
- 2 patients developed Grade 1 cytokine release syndrome (CRS); no severe adverse events such as graft-versus-host disease (GVHD) or immune effector cell-associated neurotoxicity syndrome (ICANS) were observed.  
- Grade 3–4 adverse events were limited to leukopenia, neutropenia, and lymphopenia; no severe infections occurred.  

3. Achievement of Immune Reset  
- Deep B cell depletion: Peripheral blood B cells in patients were rapidly depleted post-YTS109 infusion, with depletion lasting 1–2 months. Subsequent B cell reconstitution was dominated by immature/naive B cells.  
- Systemic immune reset: Single-cell RNA/BCR sequencing revealed that YTS109 reshaped the composition and function of immune cells. Pathogenic IGHG- and IGHA-expressing B cell populations were effectively eliminated post-infusion, while newly emerging B cell receptor (BCR) clones — distinct from baseline and dominated by IGHM and IGHD — appeared.  

4. Significant Renal Tissue Repair  
- 2 patients underwent renal pathological biopsies before and after YTS109 infusion. Results showed significant improvements in renal pathology post-infusion, including reduced glomerular cell proliferation, alleviated matrix expansion, and decreased immune complex deposition. Both IgG and C3 deposition were significantly reduced. In one patient, marked infiltration of CD20+B cells and CD8+ T cells at baseline was significantly diminished by Month 9 (M9) post-infusion, indicating substantial renal improvement.  
- Spatial transcriptomics analysis revealed that the renal microenvironment shifted toward structural repair and immune quiescence after YTS109 treatment, with reduced myeloid cell infiltration and downregulated pro-inflammatory pathways in epithelial cells — providing molecular-level evidence of localized immune remission. These findings suggest that YTS109 helps reverse the inflammatory microenvironment in affected kidneys and promotes tissue repair.  

Additionally, plasma proteomics analysis showed that the body shifted toward a state of systemic immune quiescence post-YTS109 infusion. This was accompanied by downregulation of pro-inflammatory pathways (e.g., neutrophil chemotaxis, cytokine signaling) and upregulation of pathways related to tissue repair, integrin signaling, and immune regulation. These coordinated mechanistic findings demonstrate that YTS109 not only reshapes the renal immune microenvironment but also induces broad immunomodulatory effects at the systemic level.  


Broad Clinical Prospects of YTS109  
As an "off-the-shelf" universal product, YTS109 holds broad clinical application prospects. Based on the positive results of this study, Bristar Immunotech will further expand the sample size and launch multi-center, long-term follow-up registrational clinical trials to verify YTS109’s efficacy and safety in a larger patient population — laying a solid data foundation for subsequent product registration applications.  

Meanwhile, given YTS109’s broad potential in immune reset, the team plans to expand its application to other autoimmune diseases, including autoimmune hemolytic anemia and scleroderma. Exploratory studies in these areas have already been initiated, with the goal of providing new treatment options for more patients with autoimmune conditions.  



About BriSTAR Immunotech
Founded in 2018 and led by Professor Xin Lin, a world-renowned immunologist. BriSTAR Immunotech is an innovative biotech company dedicated to developing gene-edited T cell therapies with improved efficacy and better patient accessibility, addressing key challenges in current immunocell therapy.  

The company is built on two core platforms derived from original translations of research at Tsinghua University and national laboratories: STAR-T technology and allogeneic site-specific integration technology. It has established mature teams for early-stage R&D, process development, quality control, and clinical development. To date, BriSTAR Immunotech has obtained 2 Investigational New Drug (IND) approvals in China and 1 FDA Orphan Drug Designation. It has conducted dozens of exploratory clinical studies targeting hematological malignancies, solid tumors, and severe autoimmune diseases, achieving promising safety and efficacy data. These findings have been presented at 5 prestigious international clinical conferences (including ASH, EHA, and AACR), earning high recognition from leading researchers and international peers in the field.  

Aligned with the development direction of cell therapy, BriSTAR Immunotech is actively advancing the development of universal cell therapy products, treatments for autoimmune diseases, solid tumor therapies, and new-target therapies for hematological malignancies. The company is committed to becoming a global leader in the cell therapy field, providing more innovative and effective treatment options for patients.