Universal CAR-T Cells (BRL-301) in Refractory Systemic Lupus Erythematosus

Inclusion Criteria:

1. Age range from 18 to 65 years old (including threshold), regardless of gender;

2. Subjects diagnosed with SLE according to the 2019 EULAR/ACR SLE classificationcriteria; ANA ≥ 1:80, or positive for anti dsDNA and/or anti Sm antibodies;

3. The condition becomes active again after conventional treatment is ineffective orthe disease relapses. Conventional treatment is defined as the use of two or moredrugs, including corticosteroids (more than 1mg/kg/d) and any one or more of thefollowing immunomodulatory drugs for over six months: antimalarial drugs,cyclophosphamide, azathioprine, mycophenolate mofetil, methotrexate, leflunomide,tacrolimus, cyclosporine, as well as biologics including rituximab, belimumab,etanercept, etc.

4. At least one BILAG2004 Class A or two Class B score, or both;

5. SELENA-SLEDAI score ≥ 8 points;

6. The positive expression and expression rate of CD19 on peripheral blood B cellsdetermined by flow cytometry;

7. The functions of important organs meet the following requirements: Bone marrow function needs to meet:

8. White blood cell count ≥ 3 × 109/L;

9. Neutrophil count ≥ 1 × 109/L (no Colony-stimulating factor treatment within 2weeks before examination);

10. Platelets ≥ 50 × 109/L;d. Hemoglobin ≥ 80g/L Liver function:

11. Alanine Aminotransferase (ALT) ≤ 3 × ULN;

12. Asparagus cochinchinensis transase (AST) ≤ 3 × ULN;

13. Total Bilirubin (TBIL) in serum ≤ 1.5 × ULN (excluding Gilbert syndrome, totalbilirubin ≤ 3.0 × ULN); Renal function: Creatinine Clearance Rate (CrCl) ≥ 60ml/minute (Cockcroft/Fault formula) ; Coagulation function:

14. International Normalized Ratio (INR) ≤ 1.5 × ULN,

15. Prothrombin time (PT) ≤ 1.5 × ULN. Cardiac function: good hemodynamic stability, left ventricular Ejection fraction (LVEF) ≥ 55%;

16. Female patients of childbearing potential and male patients whose female sexualpartners are of childbearing age should adopt medically recognized contraceptivemeasures or abstain from sex within at least 6 months after infusion of BRL-301;female patients of childbearing age should have a negative serum HCG test resultwithin 7 days before study enrollment and be not breastfeeding;

17. Willing to participate in this clinical study, sign an ICF, and complete follow-ups,with good compliance.

Exclusion Criteria:

1. Have a serious history of Drug allergy or allergic constitution;

2. Fungi, bacteria, viruses, or other infections that are uncontrollable or requireintravenous medication treatment exist or are suspected;

3. Active central nervous system disease caused by SLE or not (including epilepsy,psychosis, organic encephalopathy syndrome, cerebrovascular accident, encephalitis,central nervous system Vasculitis);

4. Individuals with relatively serious heart diseases, such as angina pectoris,myocardial infarction, heart failure, and arrhythmia;

5. Subjects with congenital immunoglobulin deficiency;

6. Other malignant tumors (excluding non Melanoma skin cancer, cervical cancer in situ,bladder cancer cancer and breast cancer that have survived for more than 5 yearswithout disease);

7. Subjects with end-stage renal failure;

8. Have received any of the following SLE treatments:

9. Corticosteroid (defined as prednisone or equivalent>20 mg/day) of therapeuticdose were used before enrollment or within 72 hours before BRL-301 infusion.

10. Use any other clinical study drugs for SLE within 4 weeks prior to enrollment.However, if the research treatment period is ineffective or the diseaseprogresses, and at least 3 half-lives have passed before enrollment, enrollmentis allowed.

11. Had received anti CD20 monoclonal antibody (such as Rituximab) within 4 weeksbefore screening, tetaximab within 6 weeks, or belizumab within 12 weeks.

12. Previous CAR-T cell or other genetically modified T Cell therapy.

13. Subjects with positive hepatitis B B surface antigen (HBsAg) or hepatitis B coreantibody (HBcAb) and HBV DNA titer in peripheral blood higher than the upper limitof detection; Patients with positive hepatitis C virus (HCV) antibodies and positiveperipheral blood HCV RNA; People who are positive for human immunodeficiency virus (HIV) antibodies; Those who have tested positive for syphilis;

14. Having mental illness and severe cognitive impairment;

15. Those who have participated in other clinical trials within the first 3 months ofenrollment;

16. Pregnant or intending to conceive women;

17. Patients who are unsuitable for being included into this study as deemed by theinvestigator due to other reasons.