The goal of this Phase I clinical trial is to evaluate the safety and tolerability of autologous CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy in adults with refractory systemic lupus erythematosus who have demonstrated inadequate response to standard-of-care immunosuppressive treatments.

The primary questions this study aims to address are:

What is the incidence, nature, and severity of treatment-emergent adverse events following CD19 CAR-T cell infusion? Is administration of CD19 CAR-T cell therapy feasible and tolerable in patients with refractory systemic lupus erythematosus? This study is conducted as a single-arm trial without a comparison group.

Participants will:

Undergo leukapheresis for collection of autologous peripheral blood mononuclear cells Receive a protocol-defined lymphodepleting chemotherapy regimen prior to CAR-T cell infusion Receive a single intravenous infusion of approximately 1.0 × 10⁶ CD19 CAR-T cells per kilogram of body weight Undergo scheduled clinical evaluations, laboratory testing, and longitudinal follow-up to assess safety, tolerability, and clinical parameters

This is a Phase I, single-center, open-label clinical trial evaluating the safety of autologous CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy in patients with refractory systemic lupus erythematosus (SLE).

Systemic lupus erythematosus is a chronic autoimmune disease characterized by immune dysregulation and pathogenic autoantibody production, with B lymphocytes playing a central role in disease pathophysiology. Targeting CD19-expressing B cells represents a potential therapeutic strategy for patients with disease refractory to standard immunosuppressive therapies.

Autologous CD19 CAR-T cells will be generated from peripheral blood T cells collected by leukapheresis. Cells will be genetically modified ex vivo to express a CD19-specific chimeric antigen receptor, expanded, and released for clinical administration following protocol-defined quality control testing and regulatory requirements.

Participants will receive a lymphodepleting chemotherapy regimen prior to a single intravenous infusion of CD19 CAR-T cells. Treatment administration and post-infusion monitoring will be conducted according to the protocol-specified safety and observation plan.

Following infusion, participants will be monitored for treatment-emergent adverse events, including CAR-T-associated toxicities such as cytokine release syndrome, immune effector cell-associated neurotoxicity, cytopenias, and infections. Safety evaluations will include serial clinical assessments and laboratory monitoring.

Exploratory assessments will evaluate immunological parameters, including B-cell depletion and reconstitution, autoantibody profiles, and selected biomarkers of disease activity. Participants will undergo longitudinal follow-up to assess early and delayed adverse events and the persistence of immunological effects, in accordance with regulatory guidance for gene-modified cell therapies.

Inclusion Criteria:

• Age 16 to 55 years, male or female
• Diagnosis of systemic lupus erythematosus (SLE) according to the 2019 EULAR/ACR classification criteria with a total score ≥ 10
• SLEDAI-2K score ≥ 8 at screening (with at least 4 points derived from laboratory parameters; excluding points attributable to central nervous system involvement)
• Positive antinuclear antibody (ANA ≥ 1:80) OR positive anti-dsDNA OR positive anti-Sm antibody at screening or documented in medical history

Refractory systemic lupus erythematosus or refractory lupus nephritis defined as one of the following:

Refractory SLE:

- Failure to achieve adequate response, partial response, or stable disease control after ≥ 6 months of standard-of-care therapy (documented compliance). Standard therapy includes corticosteroids plus hydroxychloroquine and at least two of the following: calcineurin inhibitors, cyclophosphamide, mycophenolate mofetil, azathioprine, or B-cell-targeted therapy (e.g., rituximab, belimumab).

Refractory Lupus Nephritis:

• Persistent active lupus nephritis after two induction regimens, including intravenous cyclophosphamide and mycophenolate mofetil administered for ≥ 6 months (with or without calcineurin inhibitors, rituximab, or belimumab), AND:

• Histopathologic confirmation of Class III or Class IV lupus nephritis, with or without Class V (ISN/RPS 2003 classification); isolated Class V is excluded

• Proteinuria > 1 g/24 hours OR urine protein-to-creatinine ratio > 1 mg/mg

• Adequate organ function:

  • ALT ≤ 5 × upper limit of normal; total bilirubin ≤ 34 μmol/L (≤ 2.0 mg/dL)
  • Pulmonary function: FVC ≥ 60% predicted OR FEV1 ≥ 60% predicted
  • Cardiac function: LVEF ≥ 50%, no uncontrolled arrhythmia, no intracardiac thrombus, no heart failure

• Adequate hematologic parameters:

  • Absolute neutrophil count ≥ 0.8 × 10⁹/L (without growth factor support)
  • Absolute lymphocyte count ≥ 0.3 × 10⁹/L
  • Platelet count ≥ 50 × 10⁹/L
  • Hemoglobin ≥ 80 g/L (≥ 8.0 g/dL)

• Ability to provide written informed consent

• Agreement to use effective contraception during the study period (for participants of reproductive potential)

Exclusion Criteria:

• History of significant neurologic disorders (e.g., traumatic brain injury, seizure disorder, hemorrhagic conditions, impaired consciousness)

• Significant cardiovascular disease within 3 months prior to screening (e.g., uncontrolled hypertension, NYHA Class III-IV heart failure, severe arrhythmia, unstable angina, myocardial infarction)

• Prior kidney transplantation

• Severe asthma requiring long-term treatment or respiratory failure

• Severe hemolytic anemia requiring transfusion at intervals ≤ 7 days

• Active viral infections (e.g., hepatitis B or C, HIV, tuberculosis, malaria, syphilis, CMV, EBV) or other life-threatening infectious diseases

• Active bacterial infection confirmed by clinical evaluation, imaging, or laboratory testing

• Use of the following prior to leukapheresis:

  • Anti-CD20 therapy, cyclophosphamide, live or attenuated vaccines within 1 month
  • Systemic corticosteroids > 10 mg/day (prednisone equivalent), T-cell-targeted therapy (e.g., mycophenolate mofetil, calcineurin inhibitors), immunosuppressive agents, or antimalarial agents within 7 days
  • Prior anti-CD19 therapy
  • Prior T-cell-based cellular therapy or gene therapy, including CAR-T therapy

• Current or prior malignancy

• Known hypersensitivity to study-related agents

• Pregnant or breastfeeding women

• Active antiphospholipid syndrome (stable antiphospholipid antibody positivity without active APS is permitted)

• Participation in another clinical trial at the time of screening

• Any condition that, in the investigator's judgment, would interfere with protocol compliance or study participation