The goal of this clinical trial is to evaluate the safety and preliminary efficacy of CD19 CAR-T cell therapy (TranspoCART19) in adults with refractory lupus nephritis. Lupus nephritis is a serious kidney complication of systemic lupus erythematosus that may not respond adequately to standard treatments.
The main questions this study aims to answer are:
* Is TranspoCART19 safe and tolerable in patients with refractory lupus nephritis? * Can TranspoCART19 induce complete or partial clinical and immunological remission?
Participants will:
* Undergo leukapheresis to collect immune cells for manufacturing TranspoCART19. * Receive lymphodepleting chemotherapy before treatment. * Receive a single fractionated infusion of TranspoCART19. * Attend regular follow-up visits for safety, disease activity, kidney function, immune response, and quality-of-life assessments for up to 24 months, with long-term safety follow-up after study completion.
Ability and willingness to provide written informed consent.
Adults aged ≥18 and ≤65 years with a diagnosis of systemic lupus erythematosus (SLE) according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria.
Positive antinuclear antibody (ANA) result at a titer >1:80, or positive anti-double stranded DNA (anti-dsDNA), or positive anti-Smith (anti-Sm) antibodies at screening.
Diagnosis of class III or IV proliferative lupus nephritis, with or without concomitant class V disease, confirmed by renal biopsy demonstrating active lupus nephritis according to the 2018 ISN/RPS classification.
Planned initiation of renal replacement therapy during the study period or eGFR <30 mL/min/1.73 m².
Left ventricular ejection fraction (LVEF) <40%.
Severe cardiac disease, including recent ischemic heart disease, NYHA class III-IV heart failure, uncontrolled arrhythmias, or severe lupus-related cardiac involvement.
Significant hepatic impairment (ALT or AST >1.5× ULN, total bilirubin >1.5× ULN except specified exceptions, INR >1.5).
Single group
TranspoCART19
Biological/VaccineAutologous CD19-directed CAR-T cell therapy administered following lymphodepleting chemotherapy. After leukapheresis and manufacturing, participants receive TranspoCART19 as a fractionated intravenous infusion (10%, 30%, and 60% of the target dose) at a total target dose of 1 × 10\^6 CAR-T cells/kg body weight. The product is manufactured using Sleeping Beauty transposon technology and consists of genetically modified T lymphocytes expressing an anti-CD19 chimeric antigen receptor.
Number of Participants With Adverse Events and Serious Adverse Events Following TranspoCART19 Infusion.
Assessment of safety and tolerability based on the incidence and severity of adverse events, serious adverse events, unacceptable toxicity, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, severe infections, prolonged cytopenias, and hypogammaglobulinemia.
Number of Participants Achieving Complete or Partial Clinical and Immunological Remission.
Proportion of participants achieving complete or partial clinical and immunological remission following TranspoCART19 infusion.
Number of Participants With Adverse Events and Serious Adverse Events During Long-Term Follow-up.
Incidence of adverse events, serious adverse events, vital sign abnormalities, physical examination findings, and laboratory abnormalities during long-term follow-up.
Change From Baseline in Hematopoietic and Immunological Reconstitution Parameters.
Changes from baseline in hemoglobin, leukocyte count, platelet count, and immune cell subpopulations including CD3+, CD4+, CD8+, CD19+ B cells, CAR-T cells, NK cells, and NKT cells.
Number and Percentage of Circulating CD19 CAR-T Cells
Number and percentage of circulating CD19 CAR-T cells in peripheral blood and their relationship with clinical response and adverse events.
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