This study is a single-arm, single-center, open-label, dose-escalation exploratory clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of CD19 CAR-γδ T cells. The subjects enrolled in this study are patients with relapsed/refractory autoimmune nephropathy, including lupus nephritis, IgA nephropathy, and membranous nephropathy. This study adopts a standard "3+3" design to assess the recommended dose (RD) and identify dose-limiting toxicities (DLTs). The treatment process is as follows: subjects who meet the inclusion criteria will receive lymphodepletion conditioning, followed by a single intravenous infusion of CD19 CAR-γδ T cells. The primary objective of this study is to evaluate the safety profile of this cellular therapy, including the incidence of DLTs, maximum tolerated dose (MTD) or RD, as well as the incidence and severity of treatment-related adverse events and clinically significant abnormal laboratory test results after CAR-γδ T cell infusion (including the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)). The planned follow-up duration of this study is 1 years.

Inclusion Criteria:

• Common Inclusion Criteria:

  1. Age ≥18 years and ≤65 years;

  2. Agree to participate in this study and sign the informed consent form;

  3. Major organ function must meet the following criteria (exceptions are allowed for abnormalities associated with active autoimmune diseases):

     1. Liver function: ALT, AST or ALP level ≤3 × ULN (upper limit of normal), bilirubin ≤2 × ULN;
     2. Renal function: eGFR ≥30 mL/min/1.73m²;
     3. Pulmonary function: blood oxygen saturation (without oxygen inhalation) ≥92%;
     4. Cardiac function: hemodynamically stable, left ventricular ejection fraction (LVEF) ≥55%;
     5. Peripheral blood function: neutrophil count ≥1×10^9/L, hemoglobin ≥60 g/L, platelets ≥30×10^9/L;

  4. Subjects of childbearing potential (including males and females) must agree to use medically acceptable effective contraceptive measures during the study period and for at least 1 year after CAR-T cell infusion.

• Primary Membranous Nephropathy:

  1. Diagnosed with primary membranous nephropathy (PMN) by renal biopsy within 18 months before screening;
  2. Meet the current clinical criteria for refractory PMN: after 6 months of systemic treatment with immunosuppressive regimens recommended by the KDIGO guidelines (including steroids, cyclophosphamide, calcineurin inhibitors, anti-CD20 monoclonal antibodies, etc.), persistent 24-hour urinary protein ≥3.5g and not reduced to less than 50% of the baseline level;
  3. Relapsed PMN: after achieving complete or partial remission with the above immunosuppressive regimens, 24-hour urinary protein re-elevated to ≥ 3.5g.

• Lupus Nephritis:

  1. Diagnosed with systemic lupus erythematosus (SLE) before screening, in accordance with the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus;
  2. Diagnosed with lupus nephritis (LN) by renal biopsy within 18 months before screening, with pathological classification consistent with ISN/RPS lupus nephritis class III/IV (with or without class V);
  3. SLEDAI-2000 score ≥6 at screening with at least 1 A grade or at least 2 B grades in the BILAG 2004 index; or SLEDAI-2000 score ≥8 at screening;
  4. Meet the current clinical criteria for refractory LN: after standardized full-dose and full-course high-dose glucocorticoid plus hydroxychloroquine therapy combined with at least 2 immunosuppressive agents of different mechanisms (cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors, etc.), or 1 immunosuppressive agent plus 1 biologic agent (belimumab, anti-CD20 monoclonal antibody, telitacicept, etc.), meet either of the following: ① After 3 months of standardized treatment, 24-hour urinary protein ≥1.5g and not reduced to less than 50% of baseline; ② After 6 months of standardized treatment, prednisone (or equivalent) cannot be tapered to 5 mg/day;
  5. Relapsed LN: after achieving complete or partial remission with induction remission therapy, disease activity re-increased during maintenance therapy, requiring re-adjustment of the treatment regimen (including increasing glucocorticoid dose or re-initiating induction remission therapy).

• IgA Nephropathy:

  1. Diagnosed with IgA nephropathy by renal biopsy within 18 months before screening;
  2. Meet the current clinical criteria for refractory IgA nephropathy: on the basis of standardized ACEI/ARB treatment, after 6 months of systemic immunosuppressive therapy recommended by the KDIGO guidelines (steroids, immunosuppressants, biologics), 24-hour urinary protein ≥0.5g and not reduced to less than 50% of baseline, or eGFR decreased by more than 50% within 3 months;
  3. Two consecutive 24-hour urinary protein measurements > 0.5g with an interval of ≥ 2 weeks after achieving clinical remission with the above immunosuppressive therapy.

Exclusion Criteria:

1. Subjects with life-threatening conditions (e.g., catastrophic antiphospholipid syndrome, acute severe renal failure) assessed by the investigator as unsuitable for enrollment in this study;
2. History of alcohol or drug abuse within 24 weeks prior to screening;
3. History of malignant tumors other than B-cell lymphoma, except for the following: malignancies confirmed to be cured or in remission for ≥5 years, radically resected basal cell carcinoma or squamous cell carcinoma of the skin, and carcinoma in situ at any site;
4. Major surgery (including joint surgery) within 24 weeks prior to screening, or planned surgery within 24 weeks after enrollment;
5. Complicated with overlapping mixed connective tissue disease, or other diseases that affect the assessment of disease activity;
6. Active hepatitis B or hepatitis C virus infection, defined as: subjects positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) with peripheral blood high-sensitivity HBV DNA quantification above the lower limit of detection; subjects with peripheral blood high-sensitivity HBV DNA quantification below the lower limit of detection may be enrolled only if the investigator provides appropriate prophylactic antiviral therapy; individuals positive for hepatitis C virus (HCV) antibody with positive peripheral blood high-sensitivity HCV RNA quantification;
7. Coinfection with human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV), Treponema pallidum, cytomegalovirus (CMV), or complicated with selective IgA deficiency;
8. Uncontrolled active infection (e.g., active pulmonary tuberculosis, etc., excluding simple urinary tract infection and bacterial pharyngitis); prophylactic administration of antibiotics, antiviral or antifungal agents is permitted;
9. Clinical signs of herpes or varicella-zoster virus infection (especially varicella, herpes zoster) within 12 weeks prior to screening;
10. History of major cardiovascular diseases within 6 months prior to screening, including NYHA class III or IV heart failure, myocardial infarction, angioplasty or stenting, unstable angina, uncontrolled or symptomatic atrial arrhythmia, any ventricular arrhythmia, or other clinically significant cardiac diseases;
11. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months prior to screening;
12. Central nervous system disorders caused by autoimmune or non-autoimmune diseases (including epilepsy, psychiatric disorders, organic brain syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis);
13. Pregnant or lactating women;
14. Hypersensitivity to any component of the CAR-γδ T cell product (including fludarabine, cyclophosphamide, tocilizumab);
15. Administration of live vaccines within 6 weeks prior to the start of conditioning therapy;
16. Participation in other clinical trials within 3 months prior to screening;
17. Any other conditions deemed by the investigator to render the subject ineligible for enrollment in this clinical trial.