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

Inclusion criteria

• Age 6-18 years old (including critical value);
• Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria;
• 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;
• SLEDAI-2000 score ≥8 points;
• Meeting the diagnosis of refractory lupus nephritis,

• 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,
• accompanied by proteinuria without remission;
• Positive expression of CD19 in peripheral blood B cells determined by flow cytometry;
• Participants had good venous access, no contraindications for cell collection;
• Participants and their guardians sign the informed consent, understand the study procedures and participate in the clinical study voluntarily;
• The functions of important organs are basically normal:

• 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;
• 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);
• Renal function: eGFR ≥30 ml/(min.1.73m2) (Schwartz formula, except abnormal renal function by SLE);
• Coagulation function:

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

Exclusion criteria

• Received kidney transplant previously;
• Serious drug allergy history or allergy;
• Presence or suspicion of fungal, bacterial, viral or other infections that cannot be controlled or require treatment;
• Complicated with severe organ dysfunction of heart, liver, lung or coagulation dysfunction;
• Complicated with congenital immunoglobulin deficiency;
• Participants with infectious diseases:

• 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;
• Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range;
• Human immunodeficiency virus (HIV) antibody positive;
• Syphilis positive;
• Diagnosed with malignant tumors in the last five years.
• Suffer from severe central nervous system disease, mental illness and severe cognitive dysfunction;
• Participated in other clinical trials within 3 months before enrollment;
• Received CAR-T therapy previously;
• Other situations that the researcher considers unsuitable for inclusion.