BCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases

Inclusion Criteria:

1. Age, 18-65 years old (inclusive), weight >=45kg, male and female;

2. The diagnosis of each disease meets the following criteria:

Systemic lupus erythematosus: 1997 ACR classification criteria or 2012 SLICC classification criteria Sjögren's syndrome: 2002 International Classification of Sjögren's Syndrome Inflammatory myopathies: 1977 Bohan Recommendation Systemic sclerosis: 1980 ACR classification criteria or 2013 ACR-EULAR classification criteria Behcet's disease: 1989 International Classification Criteria for Behcet's disease ANCA-associated vasculitis: 1990 ACR classification criteria IgG4-related disease: 2011 IgG4-RD composite diagnostic criteria Antiphospholipid syndrome: 2006 revision of the Sapporo APS classification criteria Acquired thrombotic thrombocytopenic purpura: consistent with a clinical diagnosis of TTP, including microscopic evidence of thrombocytopenia and red blood cell fragmentation (e.g., red blood cell fragmentation) 3. Multiple treatment regimens are ineffective or ineffective (including but not limited to high-dose glucocorticoids, adequate immunosuppressants and biologics) 4. Use of glucocorticoids (<=1mg/kg/d prednisone or equivalent doses of other hormones), DMARDs (such as methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil, leflunomide, cyclosporine, etc.) must be on stable treatment for 4 weeks before receiving the first study drug, and no increase in hormone dose and other immunosuppressants throughout the study.

5. Subjects voluntarily participate in this study and voluntarily sign the informedconsent form; 6. Subjects who have the possibility of having children or whosepartners have the possibility of having children must agree to use effectivecontraception throughout the study period (but cannot use oral estrogen, useestrogen vaginal ring, etc.) 7. Additional enrollment criteria for differentdiseases (related to the degree of disease activity):

6. Patients with Behcet's disease must be active patients who meet the followingconditions, and the active phase is defined as the emergence of new symptoms or thedeterioration of existing symptoms, and one of the following conditions must be met: A. Organ involvement: involvement of any major organ (e.g., ocular lesions, vascularlesions, central nervous system, gastrointestinal system); B. 100% increase in thenumber of oral or genital ulcers >=compared to the onset of oral/genital ulcerscompared to the first day; or an increase in the number of oral or genital ulcers by 3; C. Canker disease is at least 12 months; D. History of several oral ulcers permonth E. Arthritis: >=50% increase in the number of swollen joints, or 3 moreswollen joints; F. Skin lesions (non-oral/genital ulcers): >= physician overalllesion score increased by >=50% or by two points in the total score.

7. Patients with active inflammatory myopathy need to meet the following additionalconditions: Active myositis as defined by the Baseline Freehand Muscle Strength Test (MMT-8) ofno more than 125/150 and at least 2 additional CSMs that meet the criteria specifiedbelow: a) Visual Analogue Scale[VAS] of patient global activity ≥2 cm, b) physician'sglobal disease activity ≥2 cm, c) Health Assessment Questionnaire (HAQ) DisabilityIndex ≥ 0.25 d) Elevation of at least one muscle enzyme [including creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), andaspartate aminotransferase (AST)] with a minimum level of 1.3 x upper limit ofnormal e) Global Extramuscular Disease Activity Score, with a minimum of 1.0 cm on a 10 cm VAS scale [This measure is a physician's comprehensive assessment based on theassessment of physique, skin, bone, gastrointestinal, lung, and cardiac activityscale activity scores using the Myositis Disease Activity Assessment Tool (MDAAT). f) To ensure that we are able to recruit patients with active DM with severe rashwho may not meet the MMT-8 criteria above, we recommend the use of additionalinclusion criteria so that the International Myositis Assessment and Clinical Study (IMACS) Improved Definition (DOI) can be achieved: 1) MDAAT > on the 10 cm VAS scale 3 cm skin VAS score, and 2) at least 3 of the above 5 criteria.

8. ANCA-associated vasculitis: A. Comply with GPA/MPA/EGPA classification standards; B. Patients with severevasculitis activity (meeting at least one of the following conditions); a) Renal involvement is characterized by one of the following: i. Evidence ofglomerulonephritis in any of the following situations: Renal biopsy shows focalnecrotizing glomerulonephritis. Active urinary sediment characterized by glomerularhematuria and proteinuria ii. Patients with prior normal or no prior renal diseasedocument, estimated glomerular filtration rate (eGFR) <50 ml/min/1.73 m2, and priorchronic kidney disease (eGFR <60 ml/min/1.73 m2) showed a reduction in eGFR of atleast 25% compared with the previous one. b) Pulmonary hemorrhage due to active vasculitis satisfies all three of thefollowing: i. Chest X-ray or CT scan showing diffuse pulmonary infiltrates ii.Pulmonary infiltrates that cannot be explained by other causes (e.g., volumeoverload or pulmonary infection) iii. At least one of the following: Evidence ofalveolar hemorrhage on bronchoscopy or bloody bronchoalveolar lavage Hemoptysis wasobserved Unexplained anemia (<10 g/dL) or decreased hemoglobin (>1 g/dL) and lessthan 10g/dL Increased carbon dioxide dispersion

9. Additional Enrollment Criteria for Systemic Sclerosis: Subjects are at high risk of fatal outcomes based on the following prognosticfactors: Subjects must have the following "a" , and at least one of "b" or "c". a) Diffuse cutaneous scleroderma with an mRSS score of >=16, validated by the samephysician at 2 different times >= 1 day apart and separated by < 28 days. b) Presence of SSc-related lung disease with FVC < 70% or 70% predicted DLCO < afterhemoglobin correction and evidence of alveolitis obtained by high-resolution chestCT scan or PAL. c) History of SSc-related nephropathy, no disease activity before enrollmentscreening. A history of hypertensive renal crisis with scleroderma is included inthis criterion and is defined as follows: i. History of new-onset hypertension basedon any of the following (must be repeated and confirmed at least 2 hours apartwithin 3 days of the first event) with change from baseline SBP>=140 mmHg DBP>=90mmHg SBP rose by >=30 mmHg compared to baseline DBP increased by >=20 mmHg comparedto baseline AND ii. One of the following 5 characteristics Serum creatinineincreased >= >50% from baseline proteinuria: >=2+; Creatinine ratio > upper limit ofnormal Thrombocytopenia: <100, 000 plts/mm3 Hemolysis: increased by blood smear orreticulocyte count

10. Additional enrollment criteria for systemic lupus erythematosus A. The SLEDAI scoreof the patient before enrollment >= 7 points B. Failure to receive the followingtreatments: oral prednisone >=20 mg/d; Cyclophosphamide 0.4 to 0.6 g/m2 once everytwo weeks for 6 months, or other immunosuppressants such as mycophenolate mofetil 2g/day for 3 months without remission.

11. Additional enrollment criteria for antiphospholipid syndrome A. Cardiolipinantibody, lupus anticoagulant factor, and anti-β2-glycoprotein 1 antibody were allpositive before enrollment. B. History of thromboembolism or morbid pregnancy confirmed by clear objectiveevidence.

12. Sjögren's disease additional enrollment criteria A. Positive anti-Ro/SSA antibodyscreen. B. ESSDAI>= 6 POINTS

13. Additional enrollment criteria for IgG4-related diseases (confirmed: A+ B+C) A.Clinical examination showing the presence of characteristic diffuse/local swellingor masses in a single or multiple organs.

B. Blood tests show elevated serum IgG4 concentration (135 mg/dl). C. Histopathological examination shows significant lymphocytic and plasmacytic infiltration and fibrosis or IgG4+ plasmacyte infiltration (IgG4+/IgG+ cell ratio >40% and >10 IgG4+ plasma cells/HPF).

Exclusion Criteria:

1. Use of rituximab or other monoclonal antibodies within 1.6 months.

2. Received high-dose glucocorticoids (>1 mg/kg/d) within 1 month.

3. Serious complications: including heart failure (>= NYHA Class III), renalinsufficiency (creatinine clearance <=30 ml/min), hepatic insufficiency (serum ALTor AST greater than three times the upper limit of normal, or total bilirubingreater than the upper limit of normal)

4. Other severe, progressive, or uncontrollable hematologic, gastrointestinal,endocrine, pulmonary, cardiac, neurological, or cerebral diseases (includingdemyelinating diseases such as multiple sclerosis).

5. Known allergies, hyperreactivity, or intolerance to IL-2 or its excipients.

6. Have a serious infection (including but not limited to hepatitis, pneumonia,bacteremia, pyelonephritis, Epstein-Barr virus, tuberculosis infection), orhospitalization for infection, or use of intravenous antibiotics for treatment ofinfection 2 months prior to the first dose of treatment.

7. Chest imaging showing malignancy or current activity within 3 months prior to thefirst use of study drug Abnormalities in sexually transmitted infections (includingtuberculosis).

8. Infection with HIV (HIV antibody-positive serology) or hepatitis C (Hep Cantibody-positive serology).

If seropositive, it is advisable to consult a physician with expertise in the treatment of HIV or hepatitis C virus infection.

10. Any known malignancy or history of malignancy within the past 5 years (with theexception of non-melanoma skin cancer, non-melanoma skin cancer with no signs ofrecurrence or surgically cured cervical tumor within 3 months prior to the use ofthe first investigational agent).

11. Have an uncontrolled mental or emotional disorder, including a history of drug andalcohol abuse within the past 3 years, which may preclude the successful completionof the study.

12. Received or anticipated receipt of any live viral or bacterial vaccine injectionwithin 3 months prior to the first injection of study dose, during the study, orwithin 4 months after the last injection of study dose. Bacillus Calmette-Guérinvaccination within 12 months of screening.

13. Pregnant, lactating women (WCBP) who are unwilling to use medically approvedcontraception during treatment and for 12 months after the end of treatment.

14. Males whose partner is of childbearing potential but who are unwilling to useappropriate medically approved contraception during treatment and for 12 monthsafter the end of treatment.

15. Patients with inflammatory myopathies should additionally exclude: 3) Adolescent DMor PM, myositis overlaps with another connective tissue disease, cancer-associatedmyositis, inclusion body myositis, or any other non-immune-mediated myopathy.

4. Severe muscle impairment is defined as a baseline global muscle impairment score ofMDI (Myositis Injury Index) >=5cm on 10 cm VAS.

16. ANCA-associated vasculitis requires additional exceptions: positive anti-GBMantibodies.