Chimeric Antigen Receptors T Cells for Refractory/Recurrent Lupus Nephritis in Children

1. Age 6-18 years old (including critical value);
2. Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria;
3. According to the 2018 ISN/RPS LN standards diagnosed with active Class III or IV LN, with or without a membranous component and the biopsy must be performed within 6 months prior to screening;
4. SLEDAI-2000 score ≥8 points;

5. Meeting the diagnosis of refractory lupus nephritis,

   1. defined as treatment with two or more immunosuppressants (including glucocorticoids, cyclophosphamide, tacrolimus, mycophenolic acid analogues, leflunomide, and cyclosporine) for more than 6 months without inducing remission or relapse after remission,
   2. accompanied by proteinuria without remission;
6. Positive expression of CD19 in peripheral blood B cells determined by flow cytometry;
7. Participants had good venous access, no contraindications for cell collection;
8. Participants and their guardians sign the informed consent, understand the study procedures and participate in the clinical study voluntarily;

9. The functions of important organs are basically normal:

   1. Hematopoietic function (blood routine should meet):

      • Lymphocyte count ≥1×109/L,
      • White blood cell count ≥3×109/L,
      • Neutrophil count ≥1×109/L (no colony-stimulating factor treatment within 2 weeks prior to examination),
      • Hemoglobin ≥60g/L;

   2. Liver function:

      • ALT≤3×ULN (except elevated ALT caused by inflammatory myopathy),
      • AST≤3×ULN (except for elevated AST caused by inflammatory myopathy),
      • TBIL≤1.5×ULN (except Gilbert syndrome, total bilirubin ≤3.0×ULN);
   3. Renal function: eGFR ≥30 ml/(min.1.73m2) (Schwartz formula, except abnormal renal function by SLE);

   4. Coagulation function:

      • International standardized ratio (INR) ≤1.5×ULN,
      • prothrombin time (PT) ≤1.5×ULN;
   5. Heart function: hemodynamic stability;
10. Anti-nuclear antibody (ANA) ≥1:80;
11. Eastern Cancer Cooperation Group (ECOG) physical status score 0 to 2.

Exclusion Criteria:

1. Received kidney transplant previously;
2. Serious drug allergy history or allergy;
3. Presence or suspicion of fungal, bacterial, viral or other infections that cannot be controlled or require treatment;
4. Complicated with severe organ dysfunction of heart, liver, lung or coagulation dysfunction;
5. Complicated with congenital immunoglobulin deficiency;

6. Participants with infectious diseases:

   1. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBc Ab) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range;
   2. Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range;
   3. Human immunodeficiency virus (HIV) antibody positive;
   4. Syphilis positive;
7. Diagnosed with malignant tumors in the last five years.
8. Suffer from severe central nervous system disease, mental illness and severe cognitive dysfunction;
9. Participated in other clinical trials within 3 months before enrollment;
10. Received CAR-T therapy previously;
11. Other situations that the researcher considers unsuitable for inclusion.