An Exploratory Clinical Study of Anti-CD19 CAR NK Cell (KN5501) in the Treatment of Relapsed/Refractory Immune Nephropathy

Common Inclusion Criteria: 1. Age: ≥ 18 years old and ≤ 70 years old, male or female; 2. Positive CD19 expression in peripheral blood B cells as determined by flow cytometry; 3. The functions of important organs meet the following requirements: 1. Bone marrow hematopoietic function: a. White blood cell count ≥ 3 x 10\^9/L b. Neutrophil count ≥ 1 x 10\^9/L (no colony-stimulating factor treatment within 2 weeks before examination); c. Hemoglobin ≥60g/L. 2. Liver function: ALT ≤ 3 x ULN,AST≤3 x ULN, TBIL≤1.5 x ULN(excluding Gilbert syndrome, total bilirubin ≤ 3.0 x ULN) 3. Coagulation function: International standardized ratio (INR) ≤ 1.5 x ULN, prothrombin time (PT) ≤1.5 x ULN. 4. Cardiac function: good hemodynamic stability, left ventricular ejection fraction (LVEF) ≥55%. 4. Female subjects of childbearing potential and male subjects whose partner is a female of childbearing potential are required to use medically approved contraception or abstain from sex for at least 6 months during and at least 6 months after the end of the study treatment period; female subjects of childbearing potential have had a negative serum HCG test within 7 days prior to study enrollment and are not lactating; 5. Voluntarily participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up. Criteria for Recurrent/refractory primary membranous nephropathy 1. Primary membranous nephropathy diagnosed pathologically by renal biopsy; 2. Screening period 24-hour urine protein quantification ≥3.5 g; 3. Individuals who have not achieved partial remission (PR) after more than 6 months of treatment with hormonal and/or cytotoxic drugs, immunosuppressive therapy, and/or biologics (including but not limited to anti-CD20 monoclonal antibody); or individuals who have relapsed again after achieving complete remission/partial remission (CR/PR) with treatment (24h urine protein quantification ≥3.5g); 4. Glomerular filtration rate (eGFR, CKD-EPI formula) ≥45 ml/min/1.73m2 during the screening period. Criteria for Relapsed/refractory IgA nephropathy 1. Primary IgA nephropathy pathologically confirmed by renal biopsy; 2. Treated (ACEI/ARB analogs) for at least 3 months; 3. Treatment with hormonal and/or cytotoxic drugs, immunosuppressive therapy, and/or biologics (including, but not limited to anti-CD20 monoclonal antibody) for more than 6 months, 24-hour urine protein quantification ≥ 1.0 g; or rapid progression of renal function (≥ 50% decrease in eGFR within 3 months); or relapse after treatment to achieve complete remission/partial remission (CR/PR) (24-hour urine protein quantification ≥ 1.0 g); 4. Glomerular filtration rate (eGFR, CKD-EPI formula) ≥30 ml/min/1.73m2 during the screening period. Criteria for Relapsed/refractory ANCA-associated vasculitis 1. Meets 2022 ACR/EULAR diagnostic criteria for ANCA vasculitis, including microscopic polyangiitis, granulomatous polyangiitis, eosinophilic granulomatous polyangiitis; 2. Positive ANCA related antibodies (MPO-ANCA or PR3-ANCA positive); 3. Renal biopsy pathology consistent with renal damage in ANCA-associated vasculitis; 4. The Birmingham Vasculitis Activity Scale (BVAS) is ≥ 15 points (a total score of 63 points), indicating the activity of the vasculitis condition; 5. BVAS score includes at least 2 abnormalities in the renal program; 6. Definition of relapse/refractory : ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: use of glucocorticoids (more than 1 mg/kg/d) and cyclophosphamide for ≥3 months, and any of the following immunomodulatory drugs: antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, as well as biological agents such as rituximab and belimumab; 7. Glomerular filtration rate (eGFR, CKD-EPI formula) ≥15 ml/min/1.73m2 during the screening period. Common exclusion Criteria: 1. Individuals with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions; 2. Existence or suspicion of uncontrollable or treatable fungal, bacterial, viral or other infections; 3. Individuals with central nervous system disorders caused by ADs or not caused by ADs (including epilepsy, psychiatric disorders, organic encephalopathy syndromes, cerebrovascular accidents, encephalitis, central nervous system vasculitis); 4. Individuals with relatively serious heart diseases, such as angina pectoris, myocardial infarction, heart failure, and arrhythmia; 5. Subjects with congenital immunoglobulin deficiency; 6. Subjects with malignant tumors (except for non-melanoma skin cancer and in situ cervical, bladder, and breast cancers that have been disease-free for more than 5 years); 7. Subjects with end-stage renal failure; 8. Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and HBV DNA titer in peripheral blood higher than the upper limit of detection; Patients with positive hepatitis C virus (HCV) antibodies and positive peripheral blood HCV RNA; People who are positive for human immunodeficiency virus (HIV) antibodies; Those who have tested positive for syphilis; 9. Subjects with mental illness and severe cognitive impairment; 10. Subjects who have received other clinical trial treatment within 3 months; 11. Pregnant or intending to conceive women; 12. In the opinion of the investigator, there are other reasons why subjects cannot be included in this study. Exclusion Criteria for Recurrent/refractory primary membranous nephropathy 1. Secondary membranous nephropathy (e.g., hepatitis B, systemic lupus erythematosus, drug-associated, malignancy-associated, etc.), or in combination with other renal diseases confirmed by renal biopsy; 2. Type 1 or type 2 diabetes. Exclusion Criteria for Relapsed/refractory IgA nephropathy 1. Exclude secondary IgA nephropathy, including but not limited to: anaphylactic purpura, ankylosing spondylitis, systemic lupus erythematosus, desiccation syndrome, viral hepatitis, cirrhosis of the liver, rheumatoid arthritis, and mixed connective tissue disease; or in combination with other renal diseases confirmed by renal biopsy; 2. Crescentic nephritis (pathologic diagnosis of \>50% crescentic bodies), micrognathic nephropathy with IgA deposition, and other specific types of pathologic or clinical renal disease. Exclusion Criteria for Relapsed/refractory ANCA-associated vasculitis 1. Estimated glomerular filtration rate (eGFR) \<15 mL/min/1.73 m2; 2. If the patient has alveolar hemorrhage invasive lung ventilation is required, estimated to last longer than the screening period.