Anti-CD19/BCMA CAR-NK Cells in Patients With B Cell Mediated Autoimmune Disease

Inclusion Criteria: 1. Patients or their legal guardians must acknowledge the risks and procedures involved and subsequently provide informed consent to participate in the clinical trial. 2. Predicted survival time ≥ 12 weeks; 3. ECOG: 0\~2; 4. Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% ; 5. Renal function: eGFR≥30ML/min/1.73m2； (For patients with an eGFR \< 30 mL/min/1.73 m² or those receiving renal replacement therapy, inclusion or exclusion in the study is determined at the discretion of the investigators. ) 6. Liver function: Asparagus cochinchinensis transase (AST) and Alanine Aminotransferase (ALT)≤3.0 ULN, Total Bilirubin (TBIL) in serum ≤2.0×ULN; 7. Lung function: No serious lung lesions, SpO2≥92%; 8. Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-NK infusion; SLE: 1. Age:≥5 years old; 2. Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria； 3. Still in moderate to severe disease activity despite ≥3M of high dose glucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steriod ), hydroxychloroquine and at least 2 of the following treatments(cyclophosphamide, MMF, azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide, telitacicept, Beliumab, and rituximab,etc,al); or Intolerant to standard treatments; or the dosage of steroid can not be reduced to 5mg/d after 6-month of routine treatment. 4. SLEDAI 2K score\>6 points; 5. No history of Central nervous system (CNS) disease within 60 days prior to screening; 6. No history of macrophage activation syndrome (MAS) within one month prior to screening. MDR-SRNS 1. Age ≥3 years old, gender unlimited; 2. Diagnosed with SRNS according to the 2021 Kidney Disease: Improving Global Outcomes （KDIGO） Guidelines and have not achieved a complete response after 12 months of treatment with two standard doses of hormone replacement drugs with different mechanisms of action or relapse of disease activity after remission (at least one of the two drugs is a calcineurin inhibitor such as cyclosporine or tacrolimus; Other hormone replacement drugs include Mycophenolate Mofetil, cyclophosphamide, Taitacept or rituximab); Or if no remission has been achieved after 3 to 6 months of adequate treatment with one calcineurin inhibitor, if the researcher judges that the benefits outweigh the risks and the patient or guardian has fully informed consent, the patient can be considered for inclusion.Patients with other diseases, such as systemic lupus erythematosus, requiring long-term systemic treatment with glucocorticoids or immunosuppressants, may be considered for inclusion after the investigator determines that the benefits outweigh the risks and the patient or guardian has fully informed consent; 3. Renal biopsy was performed and the pathological type was determined to be minimal lesion nephropathy(MCD) or focal segmental glomerulosclerosis (FSGS); IgA nephropathy 1. Age: ≥ 5 years old, male or female; 2. IgA nephropathy pathologically confirmed by renal biopsy; 3. Angiotensin-Converting Enzyme Inhibitors (ACE) or angiotensin receptor blocker (ARB) treated for at least 3 months and meet at least one of the following requirements: 1. Combination or sequential treatment with steroids and at least one immunosuppressant or biologic for ≥ 3 months; and 24-hour urine protein quantification ≥500mg or UPCR≥0.5mg/mg; 2. \>50% decline in eGFR within 3 months; 3. Patients who are unable to tolerate conventional treatment and for whom the investigator determines the benefits outweigh the risks and who have obtained fully informed consent from the patient or guardian may be considered for inclusion; 4. Exclude subjects with other secondary causes; exclude patients with uncontrolled blood pressure. Exclusion Criteria: 1. Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, obinutuzumab), or subjects with a history of severe allergic reactions 2. Uncontrollable infection, or active infection that requires systemic treatment within 1 week prior to screening； 3. Subjects with grade III or IV heart failure (NYHA classification) 4. Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs； 5. Renal replacement therapy has been or is being performed within 3 months prior to transfusion; 6. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive; 7. Signs of herpes or varicella-zoster virus infection (especially chickenpox, shingles) within 12 weeks prior to screening; 8. Patients had seizure, or other active central nervous system disease; 9. Patients with malignant diseases such as tumors before screening, or with other serious life-threatening diseases; 10. Secondary or congenital immunodeficiency. 11. History of any cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal disease or other major medical condition that would prevent the administration of KN5601, except for lupus (determined by the investigator) 12. Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening; Acute graft-versus-host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening; 13. Received live vaccine within 4 weeks before screening; 14. Subjects who have received B cell-targeted drug therapy within 1 month before enrollment 15. Tested positive in Blood pregnancy test； 16. Patients who participated in other clinical study within 3 months prior to enrollment; 17. Any abnormal laboratory test results judged by the investigator to be clinically significant and prevent the subject from participating in the study. Laboratory test values that are out of range and not of clinical significance will not be considered as exclusion criteria 18. Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome