CD19-Directed CAR-T Cell Therapy in Refractory Systemic Lupus Erythematosus

Prior treatment

• Clinically significant cardiovascular disease, including NYHA Class III/IV heart failure, myocardial infarction, unstable arrhythmias, or unstable angina within the previous 6 months.
• Active neurological disease (stroke, epilepsy, or neurodegenerative disorders) within the previous 12 months.
• Previous or suspected hemophagocytic lymphohistiocytosis/macrophage activation syndrome.
• Major surgery within 4 weeks prior to screening.
• Administration of a live attenuated vaccine within 4 weeks prior to screening.
• Prior allogeneic or autologous hematopoietic stem cell transplantation or prior solid organ transplantation.

Other illness

• Severe pulmonary hypertension (estimated pulmonary artery systolic pressure \>50 mmHg).
• History of malignancy within 2 years prior to screening, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, ductal carcinoma in situ of the breast, or stage I uterine cancer.
• Active or uncontrolled bacterial, viral, fungal, or other infection.
• Active hepatitis B infection or detectable HBV DNA.
• Active hepatitis C infection or detectable HCV RNA.
• Human immunodeficiency virus (HIV) infection.
• Any medical condition that, in the investigator's judgment, could compromise participant safety or interfere with study assessments.

Other

• Requirement for systemic anticoagulation at screening.
• Pregnancy, breastfeeding, or plans to become pregnant during the study or within 12 months after CAR-T cell infusion.
• Inability or unwillingness to comply with study procedures and follow-up requirements.

• Adults aged 18 to 50 years, inclusive.
• Diagnosis of systemic lupus erythematosus (SLE) according to the 2019 ACR/EULAR classification criteria.
• Active disease at screening, defined as SLEDAI-2K ≥4 and Physician Global Assessment (PGA) ≥0.5.
• Inadequate response, intolerance, or contraindication to corticosteroids and at least two of the following therapies: azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate, belimumab, rituximab, or tacrolimus.
• Adequate organ function, including:
  • Hepatic function: AST and ALT ≤3× upper limit of normal (ULN); total bilirubin ≤2× ULN (participants with documented Gilbert syndrome are eligible).
  • Hematologic function: neutrophils ≥1,000/mm³; hemoglobin ≥8 g/dL without transfusion within 14 days; lymphocytes ≥500/mm³; platelets ≥20,000/mm³ without transfusion within 14 days.
  • Renal function: estimated creatinine clearance ≥30 mL/min (CKD-EPI).
  • Cardiac function: left ventricular ejection fraction ≥40%.
  • Pulmonary function: oxygen saturation ≥92% on room air.
• Women of childbearing potential must agree to use highly effective contraception during study participation and for 12 months after CAR-T cell infusion.
• Male participants must agree to use barrier contraception during study participation and for 12 months after CAR-T cell infusion.
• Ability to understand and provide written informed consent.