Study of Therapeutic Efficacy of Anti-CD19 CAR-T Cells in Refractory Systemic Lupus Erythematosus

Prior treatment

• Prior Cell Therapy: Previous treatment with any CAR-T cell therapy or other genetically modified effector cell products.
• Severe Renal Impairment and Fibrosis:
  • Receiving renal replacement therapy (dialysis) within 3 months prior to infusion.
  • Irreversible Renal Damage: Documented high chronicity on baseline biopsy (e.g., Chronicity Index \>6/12) or extensive renal fibrosis, as these patients are unlikely to achieve functional recovery despite immunological remission.
  • Significant nephropathy likely requiring high-dose glucocorticoids (≥1mg/kg/day prednisone or equivalent) or intensified DMARDs within 3 months of infusion.
• Concomitant Therapy: Requirement for long-term glucocorticoids or immunosuppressive therapy for conditions other than SLE.
• Infections: Active infections requiring systemic treatment or uncontrollable infections (bacterial, fungal, or viral) within 1 week before screening.
• Transplantation/GVHD: Solid organ or hematopoietic stem cell transplantation within 3 months before screening; or presence of Grade 2 or higher acute graft-versus-host disease (GVHD) within 2 weeks of screening.
• Other Clinical Conditions:
  • Macrophage activation syndrome (MAS) within 1 month before screening.
  • Vaccination with a live vaccine within 4 weeks before screening.
  • Malignancies or other severe systemic diseases.
• Trial Participation: Enrollment in another clinical trial within 3 months prior to this study.

Other illness

• Neurological/CNS Involvement:
  • Active central nervous system (CNS) lupus requiring clinical intervention within 60 days of screening (including seizures, delirium, or cerebrovascular events).
  • Evidence of significant structural CNS damage on MRI or a history of severe seizures that may lower the threshold for ICANS.
• Cardiac Conditions:
  • Serious congenital heart disease; acute myocardial infarction within 6 months of screening; severe arrhythmias (e.g., multifocal premature ventricular tachycardia); large pericardial effusion; severe myocarditis; or hypotension requiring pressor agents at screening.
• Pulmonary Pathology:
  • History of severe lung disease, including significant bronchiectasis, emphysema, or advanced interstitial lung disease (ILD) at baseline.
  • Resting oxygen saturation (SpO2 \<92%).
• Viral and Serological Markers:
  • Positive HBsAg or HBcAb with detectable HBV-DNA.
  • Positive HCV antibody with detectable HCV-RNA.
  • Positive HIV antibody, syphilis test, or detectable CMV-DNA.
• Investigator Discretion: Any other condition that, in the opinion of the investigator, makes the subject unsuitable for the study or puts them at undue risk.

Other

• Pregnancy: Positive blood pregnancy test at screening.

• Age: ≥5 years old.
• Refractory SLE Diagnosis:
  • Diagnosed with SLE according to the 2019 EULAR/ACR classification criteria.
  • Exhibit persistent moderate to severe disease activity (defined as a SLEDAI-2K score ≥ 8).
  • Demonstrated failure or to achieve target disease control (LLDAS or remission) after a minimum of 6 months of standard-of-care therapy, including: high doses of glucocorticoids (≥1mg/kg/day prednisone or equivalent), hydroxychloroquine, and at least two DMARDs (including cyclophosphamide, MMF, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide, tocilizumab, belimumab, and rituximab) for at least 6 months; or intolerant to conventional treatments.
  • Note: Patients may also be eligible if they are documented as intolerant to these conventional treatments.
• Disease Severity Validation: To ensure a "refractory" status, patients must satisfy at least one of the following:
  • Active Major Organ Involvement (e.g., biopsy-proven Lupus Nephritis Class III, IV, or V; CNS lupus; or refractory hematological cytopenias).
  • Steroid Dependence: Inability to taper glucocorticoid dose below 0.5 mg/kg/day (or equivalent) without a disease flare.
• Organ Function:
  • Cardiac: LVEF ≥ 55 %, with no significant clinical abnormalities on ECG.
  • Renal: Estimated glomerular filtration rate (eGFR) 30 mL/min/1.73m2.
  • Liver: AST and ALT ≤ 3.0 ULN, and total bilirubin ≤ 2.0 ULN.
  • Pulmonary: No severe lung disease, with oxygen saturation (SpO2) ≥ 92% on room air.
• Apheresis Suitability: Must meet institutional criteria for leukapheresis and have no contraindications to peripheral blood mononuclear cell (PBMC) collection.
• Contraception: Females of childbearing age must have a negative urine pregnancy test at screening and agree to use effective contraceptive measures from enrollment until 1 year after MC-1-50 cell infusion.
• Informed Consent: Voluntary written informed consent must be obtained from the subject (if applicable) and their lawful guardians prior to any screening procedures.