We report the first case of STAR-T (Synthetic TCR and Antigen Receptor), an innovative allogeneic T cell product with TCR site-specific integration and novel knockout strategies, administered without lymphodepletion in refractory SLE/LN, representing a paradigm shift toward safer cellular immunotherapy.

A 39-year-old female with 13-year SLE history met refractory SLE/LN criteria for clinical trial (NCT06978647). Despite extensive therapy (corticosteroids, cyclophosphamide, hydroxychloroquine, mycophenolate mofetil, cyclosporine), she demonstrated treatment-refractory disease. Baseline: active renal involvement with urine protein 1.79g/24h, renal biopsy confirming Class III lupus nephritis with activity/chronicity index (AI/CI) 3/3. The patient received allogeneic STAR-T cells at 3×10⁶ cells/kg without lymphodepletion. Corticosteroids tapered from 6mg to 4mg post-infusion. Regular monitoring was conducted to evaluate the safety, PK/PD and efficacy outcomes as per the study protocol. 

The patient demonstrated rapid and profound therapeutic response. Proteinuria dramatically improved from baseline 1.79 g/24h to 0.71 g/24h by day 28, achieving partial remission (PR) within one month. Most remarkably, complete remission (CR) with proteinuria <0.5 g/24h was achieved by M2 and sustained through M3. Immunological parameters normalized rapidly, with complement C3 recovery by day 14 post-infusion. Disease activity assessment showed substantial improvement: SLEDAI-2K score decreased from 6 to 2 points, PGA reduced from 1 to 0.5 points. The patient achieved remission according to DORIS criteria. STAR-T demonstrated potent expansion kinetics with peak copy number of 412 copies/μg DNA on day 4, confirming effective engraftment without lymphodepletion. B-cell depletion was achieved. No CRS or ICANS observed throughout treatment. Now the patient remains under follow-up observation.

This case demonstrates that STAR-T therapy with TCR site-specific integration and innovative knockout strategies can achieve effective in vivo expansion and clinical remission in refractory SLE/LN without lymphodepletion. This provides crucial direction for future non-lymphodepleting cellular therapy research. While this single case provides proof-of-concept, findings cannot establish generalizability. The patient's baseline lymphocyte count of 0.77×10⁹/L may have contributed to favorable response. Systematic studies are essential to investigate non-lymphodepletion T therapy, including T cell product optimization, precision patient selection, and larger case series.