Dual Target CAR-T Cell Treatment for Refractory Systemic Lupus Erythematosus (SLE) Patients

Inclusion Criteria:

1. 18-70 years old;

2. Total score ≥ 10 on the EULAR/ACR 2019 SLE classification criteria;

3. LLDAS response criteria are not achieved after administration with at least twoimmunosuppressants (including, but not limited to, azathioprine, mycophenolatemofetil, cyclophosphamide, methotrexate, leflunomide, tacrolimus, ciclosporin andiguratimod) and/or at least one approved biological agent for more than 6 months.

4. SELENA-SLEDAI≥8;

5. Patients with CD19+ B-cell;

6. Hemoglobin≥85 g/L;

7. WBC≥2.5×10^9/L

8. NEUT≥1×10^9/L;

9. BPC≥50×10^9/L;

10. AST/ALT below 2 times the upper limit of normal; Creatinine clearance ≥30 mL/min;blood bilirubin ≤2.0 mg/dl; echocardiography indicates that the ejection fraction is ≥50%;

11. Adequate venous access for apheresis, and no other contraindications forleukapheresis;

12. Women of childbearing age should have a negative serum or urine pregnancy test atscreening and baseline. Subjects agree to take effective contraceptive measuresduring the trial until at least 1 year after CAR-T cells infusion.

13. Agree to attend follow-up visits as required;

14. Voluntary participation and informed consent signed by the patient or his/herlegal/authorized representative;

Exclusion Criteria:

1. Renal disease: severe lupus nephritis (serum creatinine > 2.5 mg/dL or 221 μmol/L)within 8 weeks prior to leukapheresis, or subjects who need hemodialysis;

2. CNS disease: including epilepsy, psychosis, organic encephalopathy syndrome,cerebrovascular accident [CVA], encephalitis or CNS vasculitis, psychiatric patientswith depression or suicidal thoughts;

3. Patients with serious lesions and history of present illness of vital organs such asheart, liver, kidney and blood and endocrine system;

4. Patients with immunodeficiency, uncontrolled active infections and active orrecurrent peptic ulcers;

5. Received immunosuppressive therapy within 1 week prior to leukapheresis;

6. Patients with HIV infection; Active infection of hepatitis B virus or hepatitis Cvirus; Patients with syphilis infection;

7. The presence or suspicion of an active fungal, bacterial, viral or other infectionthat cannot be controlled during screening;

8. Received live vaccine treatment within 4 weeks prior to screening;

9. Severe allergies or hypersensitivity;

10. Contraindication to cyclophosphamide in combination with fludarabine;

11. Subjects who have undergone major surgery within 2 weeks prior to signing theinformed consent form, or who are scheduled to have surgery (other than localanesthetic surgery) during the trial or within 2 weeks of the infusion;

12. cannula or drainage tubes other than central venous catheters;

13. Pregnant or lactating women, or subjects who plan to have children within 1 year oftreatment;

14. Subjects with prior CD19 or BCMA-targeted therapy

15. Participated in any clinical study within 3 months prior to enrollment

16. Subjects with malignant tumour, except for Non-melanoma Skin Cancer with PFS>5yr;Cervical Cancer in situ; Bladder Cancer; Breast Cancer;

17. Any situations that the investigator believes the patients are not suitable for thestudy.