Abstract: SA-PO0813
Off-the-Shelf Dual-Targeted Synthetic T-Cell Receptor (STAR-T) for Autoimmune Kidney Diseases: Preclinical Proof of Concept and First Clinical Experience
Session Information
- Glomerular Diseases: Management, Evolving Strategies, and Practice-Changing Advances
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Lei, Lei, Bristar Immunotech Limited, Beijing, China
- Li, Yang, Bristar Immunotech Limited, Beijing, China
- Dongmei, Y., Bristar Immunotech Limited, Beijing, China
- Yu, Yadi, Bristar Immunotech Limited, Beijing, China
- Wang, Shuai Wang, Bristar Immunotech Limited, Beijing, China
- Zheng, Hongli, Bristar Immunotech Limited, Beijing, China
- Zhao, Xueqiang, Bristar Immunotech Limited, Beijing, China
- Lin, Xin, Tsinghua University School of Medicine, Beijing, China
Background
Refractory autoimmune kidney diseases including lupus nephritis (LN), IgA nephropathy (IgAN), and membranous nephropathy (MN) are leading causes of end-stage renal disease, with limited treatment options after standard immunosuppressive and/ or biological therapy failure. While autologous B-cell targeted CAR-T therapy has shown preliminary efficacy, its clinical application is limited, particularly in patients with acute progression, by long manufacturing cycles, high costs, and inconsistent cell quality. We developed an off-the-shelf dual-targeted synthetic T cell receptor (STAR-T) product to overcome these limitations, and have completed preclinical proof-of-concept as well as initial clinical infusions.
Methods
We constructed a dual-targeted STAR-T product targeting CD19 and BCMA, featuring TRAC locus disruption to eliminate endogenous TCR expression (mitigating GvHD risk), along with HLA-A/B, CIITA and R gene knockout to confer resistance to host T cell rejection. Preclinical efficacy and safety were validated in B-cell lines and xenograft models. The investigator-initiated phase 1 trials were initiated to evaluate the product in refractory autoimmune kidney diseases.
Results
In preclinical studies, our dual-targeted STAR-T product effectively depleted CD19+ or BCMA+ B cells, with superior cytotoxic activity compared to single-target STAR-T. To date, two patients with refractory LN failing multiple therapies have received the investigational product. Preliminary data provide early evidence of safety and efficacy for dual-targeted STAR-T in treating autoimmune kidney disease.
Conclusion
Our off-the-shelf dual-targeted STAR-T product has shown robust preclinical activity, and initial clinical experience supports its safety for further development. This off-the-shelf product eliminates wait times for personalized autologous manufacturing, providing an accessible novel therapy for patients with refractory autoimmune kidney diseases. Further enrollment and follow-up are ongoing to confirm long-term safety and efficacy in autoimmune kidney disease.