CAR-T Therapy for Refractory Autoimmune Diseases

Inclusion Criteria:

1. Age ≥18 years old, regardless of gender, signed with informed consent (ICF).

2. Diagnosed as one of the following diseases: Systemic lupus erythematosus (SLE)；Sjogren's syndrome (SS) ; Systemic Scleroderma (SSc); Dermatomyositis (DM);Anti neutrophil cytoplasmic antibody associated vasculitis (ANCA-AAV).

3. Patients who have been treated with ≥ 2 immunosuppressive agents for 3 months, orrequire ≥ 15mg glucocorticoids to maintain stable condition, or are intolerant tostandard treatment, or have relative contraindications, and whose disease activitymeets the following criteria:

4. For SLE patients, SLEDAI ≥ 8 points;

5. For SS patients, Sjogren's syndrome disease activity index(ESSDAI )≥ 14 points;

6. For SSc patients, the modified skin score (mRSS) score ranges from 10 to 35 (including cutoff values) and is associated with interstitial pneumonia (ILD);

7. For DM patients, diagnosed for at least 1 year;

8. For ANCA-AAV patients, Birmingham Vasculitis Activity Score(BVAS) score ≥ 15and ANCA antibodies.

9. Eastern Cooperative Oncology Group(ECOG) 0-1 points;

10. The evaluation of important organ functions meets the following conditions:

11. Blood count: hemoglobin ≥ 60g/L, platelet count ≥ 30 × 109/L;

12. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 55%, nosignificant abnormalities observed on electrocardiogram;

13. Renal function: estimated glomerular filtration rate(eGFR) ≥ 30 mL/min/1.73m2;

14. Liver function: Aspartate Aminotransferase(AST) and Alanine Transaminase(ALT) ≤ 3.0 upper limit of normal(ULN), total bilirubin ≤ 2.0 ULN;

15. Pulmonary function: diffusion capacity of the lung for carbon monoxide(DLCO) ≥ 40% expected value; forced vital capacity(FVC) ≥ 50% of expected value;

16. Having single or intravenous blood collection standards and no othercontraindications for cell collection;

17. The urine pregnancy test results of subjects of childbearing age are negative, andthey agree to take effective contraceptive measures during the trial period, untilone year after infusion;

18. The patient or their guardian agrees to participate in this clinical trial and signsan informed consent form, indicating their understanding of the purpose andprocedures of this clinical trial and willingness to participate in the study.

Exclusion Criteria:

1. Previously received Chimeric Antigen Receptor T cell(CAR-T) therapy;

2. Suffering from severe diseases of the heart, liver, lungs, blood system, andendocrine system, the researcher has determined that the risk of participating inthe trial is higher than the benefit;

3. Active or uncontrollable infections that require systemic treatment within the firstweek of screening;

4. Previously received hematopoietic stem cell transplantation or solid organtransplantation (excluding corneal and hair transplantation), or screened for acutegraft-versus-host disease (GVHD) with grade 2 or above in the first two weeks;

5. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) is positiveand the hepatitis B virus(HBV) DNA titer in peripheral blood is greater than thenormal reference value; Or hepatitis C virus (HCV) antibody positive and peripheralblood HCV RNA titer detection greater than the normal reference range; Or positivefor human immunodeficiency virus (HIV) antibodies; Or those who test positive forsyphilis; Or positive for cytomegalovirus (CMV) DNA detection;

6. Received live vaccine within 4 weeks prior to screening;

7. Pregnancy test positive individuals;

8. Patients with malignant tumors and other malignant diseases before screening, inaddition to fully treated cervical cancer in situ, basal cell or squamous cell skincancer, local prostate cancer after radical surgery, and ductal carcinoma in situafter radical surgery;

9. Screening patients who have participated in other clinical trials within the firstthree months;

10. Other researchers believe that it is not suitable to participate in this study.