An Exploratory Clinical Study on the Safety and Efficacy of CD19/BCMA Chimeric Antigen Receptor NK Cells in the Treatment of B Cell-related Autoimmune Diseases in Children
this is an investigator-initiated trial aimed at evaluating the efficacy and safety of anti-CD19/BCMA CAR-NK Cells in Patients With B cell mediated autoimmune disease.
• Patients or their legal guardians must acknowledge the risks and procedures involved and subsequently provide informed consent to participate in the clinical trial.
• Predicted survival time ≥ 12 weeks;
• ECOG: 0\
∙ 2;
• Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram;
• 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. )
• Liver function: Asparagus cochinchinensis transase (AST) and Alanine Aminotransferase (ALT)≤3.0 ULN, Total Bilirubin (TBIL) in serum ≤2.0×ULN;
• Lung function: No serious lung lesions, SpO2≥92%;
• Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-NK infusion;
∙ SLE:
• Age:≥5 years old;
• Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria;
• 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); or Intolerant to standard treatments; or the dosage of steroid can not be reduced to 5mg/d after 6-month of routine treatment.
• SLEDAI 2K score\>6 points;
• No history of Central nervous system (CNS) disease within 60 days prior to screening;
• No history of macrophage activation syndrome (MAS) within one month prior to screening.
∙ MDR-SRNS
• Age ≥3 years old, gender unlimited;
• 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;
• Renal biopsy was performed and the pathological type was determined to be minimal lesion nephropathy(MCD) or focal segmental glomerulosclerosis (FSGS);
∙ IgA nephropathy
• Age: ≥ 5 years old, male or female;
• IgA nephropathy pathologically confirmed by renal biopsy;
• 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:
‣ 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;
⁃ ≥ 50% decline in eGFR within 3 months;
⁃ 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;
• Exclude subjects with other secondary causes; exclude patients with uncontrolled blood pressure.