Universal STAR-T Cell Injection in Autoimmune Kidney Diseases

Inclusion criteria

• Subjects must meet all the following inclusion criteria to be enrolled in this study:

• Age 18-65 years (inclusive), gender (no gender restriction);
• Previous diagnosis of IgA Nephropathy (IgAN) or Primary Membranous Nephropathy (PMN)：

• IgA Nephropathy (IgAN): Renal biopsy confirmed as IgAN, and meets any one of the following criteria:

• Treatment-refractory IgAN: Previously received RAAS inhibitors or SGLT2 inhibitors or endothelin receptor antagonists (ERA) or mineralocorticoid receptor antagonists (MRA) for at least 12 weeks, and combined with/or sequentially added at least one immunosuppressant or biologic agent for ≥3 months, with 24-hour urinary protein ≥1.0 g or 24-hour urine protein/creatinine ratio (UPCR) ≥0.8 g/g;
• eGFR decreased by ≥50% within the past 3 months, and acute kidney injury (AKI) is excluded;
• Unable to tolerate conventional treatment, may be considered for enrollment after full evaluation by the investigator.
• Primary Membranous Nephropathy (PMN): Renal biopsy confirmed as PMN, and anti-phospholipase A2 receptor antibody (anti-PLA2R) is positive, and meets any one of the following criteria for relapsed or refractory PMN:

• Refractory PMN: Received hormone combined with cyclophosphamide or calcineurin inhibitor (CNI) or rituximab for ≥6 months, and meets any one of the following:(a) Anti-PLA2R persistently high titer >50 RU/mL;(b) Persistent 24-hour urinary protein >3.5 g/d, and reduction <50% during treatment;(c) Unable to tolerate the above immunosuppressive therapy, or discontinued due to severe adverse reactions;
• Relapsed PMN: After achieving complete remission, 24-hour urinary protein re-increased to >3.5 g/d;
• Function of vital organs meets the following requirements:

<!-- -->

• Bone marrow function must satisfy:(a) Neutrophil count ≥1.0×10⁹/L (without colony-stimulating factor treatment within 2 weeks prior to testing, except for disease-induced neutropenia);(b) Hemoglobin ≥60 g/L;(c) Platelet count ≥30×10⁹/L;
• Liver function:(a) ALT ≤3×ULN (elevations due to disease are excluded);(b) AST ≤3×ULN (elevations due to disease are excluded);(c) TBIL ≤1.5×ULN (elevations due to disease are excluded);
• Kidney function: Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² (calculated by CKD-EPI formula);
• Coagulation function: International Normalized Ratio (INR) ≤1.5×ULN, Prothrombin Time (PT) ≤1.5×ULN;
• Cardiac function: Hemodynamically stable; 4. Female subjects of childbearing potential and male subjects whose partners are of childbearing potential must agree to use medically accepted contraceptive measures or abstinence during the study and for 24 months after cell infusion; female subjects of childbearing potential must have a negative serum HCG test within 7 days prior to enrollment and must not be lactating: 5. Voluntarily participate in this clinical study and sign the informed consent form.

Exclusion criteria

• Subjects who meet any of the following exclusion criteria will be excluded from this study:

• Secondary IgAN, secondary membranous nephropathy;
• Use of immunosuppressive agents with therapeutic effect on the disease within five half-lives prior to cell infusion, or biologics within 4 weeks;
• History of severe drug allergy or allergic constitution;
• Uncontrolled or requiring treatment fungal, bacterial, viral, or other infections;
• Active tuberculosis at screening;
• Cardiac insufficiency (NYHA functional class >II), unable to tolerate study lymphodepletion and cell reinfusion;
• Subjects with congenital immunoglobulin deficiency;
• History of malignant tumor within the past 5 years that has not yet resolved;
• Positive for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer above the detection limit; positive for hepatitis C virus (HCV) antibody with peripheral blood HCV RNA positive; positive for human immunodeficiency virus (HIV) antibody; positive for syphilis test;
• Male and female subjects who plan to conceive during the study period or within 24 months after cell infusion;
• Subjects whom the investigator deems otherwise unsuitable for inclusion in this study.