Universal CAR-T Cell Therapy for Refractory Lupus Nephritis

A Clinical Study of the Safety and Efficacy of Universal CAR-T Cells Targeting BCMA and CD19 for the Treatment of Refractory Lupus Nephritis

This investigator-initiated trial aims to assess the efficacy and safety of combination therapy using universal CAR-T cells targeting BCMA and CD19 in refractory lupus nephritis.

This study is a non-randomized, open-label, single-arm clinical trial designed to assess the efficacy and safety of combination therapy for refractory lupus nephritis using universal CAR-T cells targeting BCMA and CD19.

Inclusion Criteria:

• Aged 18-65 years; both genders eligible.
• Subjects diagnosed with lupus nephritis.
• Previous treatment outcomes were unsatisfactory.
• Diagnosis of active nephritis type III or IV with or without type V according to 2018 International Society of Nephrology and Society of Renal Pathology (ISN/RPS) criteria.
• NIH Activity Index > 2 and elevated chronicity index.
• Urine protein: creatinine ratio (UPCR) ≥ 1.0 g/g, or 24-hour urine protein ≥ 1.0 g, with or without active urine sediment with red blood cell casts.
• Receiving hormones with or without antimalarials.
• SLEDAI-2K score ≥ 6.
• Antinuclear antibody positive, and/or anti-ds-DNA antibody positive, and/or anti-Smith antibody positive.
• Positive expression of CD19 on B cells in peripheral blood.
• Agrees to use double barrier methods, condoms, oral or injectable contraceptives, or intrauterine devices during the study period and for one year after taking the study medication.
• Provides written informed consent.

Exclusion Criteria:

• History of solid organ transplantation.
• Malignant tumor within the last two years.
• Positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb), with peripheral blood Hepatitis B virus (HBV) DNA detected as positive; positive for Hepatitis C virus antibodies, with peripheral blood Hepatitis C virus RNA detected as positive; positive for Human Immunodeficiency Virus (HIV) antibodies; positive for Cytomegalovirus (CMV) DNA; positive for syphilis.
• Primary immunodeficiency (congenital or acquired).
• Severe cardiac disease.
• History of psychiatric disorders or history of psychotropic drug abuse, with no history of withdrawal.
• Allergic constitution or a history of severe allergies.
• Pregnant or breastfeeding women.