Abstract: SA-PO0808
Allogeneic CD19 Synthetic T-Cell Receptor (STAR-T) Without Lymphodepletion for Refractory Lupus Nephritis: First-in-Human Result
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
- Sun, Fei, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- Zheng, Hongli, Bristar Immunotech.cn, Beijing, China
- Lei, Lei, Bristar Immunotech.cn, Beijing, China
- Zhao, Xueqiang, Bristar Immunotech.cn, Beijing, China
- Lin, Xin, Department of Basic Medical Sciences, Tsinghua University School of Medicine, Beijing, China
- Zhu, Jian, The First Medical Center, Chinese PLA General Hospital, Beijing, China
Background
Systemic lupus erythematosus with lupus nephritis (SLE/LN) remains a clinical challenge despite conventional immunosuppressive therapy. While chimeric antigen receptor (CAR-T) cell therapy has shown promise for refractory autoimmune diseases, current protocols still rely on pre-conditioning lymphodepletion, which brings significant safety risks and limits large-scale clinical translation. This study reports the first application of allogeneic STAR-T (Synthetic TCR and Antigen Receptor) cells - an innovative T cell product with TCR site-specific integration and a novel gene knockout strategy - in the treatment of refractory LN without lymphodepletion.
Methods
We constructed an off-the-shelf CD19-targeted allogeneic STAR-T product: TRAC locus editing eliminated endogenous TCR expression to mitigate of graft-versus-host disease (GvHD) risk; we identified R gene via CRISPR knockout screening as a key target overcoming host-versus-graft reactivity (HvGR), and combined it with HLA-A knockout to enable STAR-T cells to resist host T cell rejection. Preclinical activity was evaluated via assays including co-culture with allogeneic PBMCs and assessing the lysis of primary B cells. We initiated a clinical trial (NCT06978647) enrolling refractory SLE patients, and the first case has been completed per protocol.A 39-year-old female with 13-year refractory SLE (refractory to multiple therapies) and active Class III lupus nephritis at baseline received a single infusion of allogeneic STAR-T (3×10^6 cells/kg) without lymphodepletion. Safety and efficacy were monitored per protocol.
Results
Preclinically, R gene knockout CD19 STAR-T cells resisted allogeneic PBMC -mediated killing and effectively eliminated primary B cells.
Clinically, the patient achieved a rapid, profound therapeutic response with excellent safety: Complement C3 recovery by day 14, Proteinuria decreased to 0.71g/24h (partial remission) by day 28, and complete remission was reached at month 2, and overall response met DORIS remission criteria. STAR-T cells showed expansion, confirming effective engraftment without lymphodepletion, with complete B-cell depletion achieved. No CRS or ICANS was observed.
Conclusion
This is the first report of non-lymphodepletion allogeneic STAR-T achieving effective engraftment. Our trial is ongoing in larger cohorts and to confirm this off-the-shelf product’s potential for autoimmune disease therapy.
Funding
- Commercial Support – Bristar Immunotec liminted