An Exploratory Clinical Study of SCAR02 Targeting BCMA and CD19 for the Treatment of Refractory Autoimmune Diseases

Inclusion Criteria:

1. Sign the informed consent form.

2. At the time of signing the informed consent form, the age of 18 years old or above,both male and female.

3. Bone marrow hematopoietic function is satisfied: white blood cell count ≥3×10^9/L;neutrophil count ≥1×10^9/L (not receiving colony-stimulating factor within 2 weeksprior to screening); hemoglobin ≥60g/L.

4. Liver function fulfillment: ALT≤3×ULN; AST≤3×ULN; TBIL≤3×ULN.

5. Renal function fulfillment: creatinine clearance CrCl ≥ 60mL/min.

6. Coagulation function meets: international standard ratio INR <1.5 times ULN,prothrombin time PT <1.5 times ULN.

Patients with rheumatoid arthritis must also meet the following enrollment criteria:

1. Diagnosis of rheumatoid arthritis according to the 2010 ACR / EULAR diagnosticcriteria.

2. Fulfillment of one of the following conditions: DAS28-ESR >3.2 or CDAI >10 at 3months after use of a standard treatment regimen prior to screening; inability totaper hormones (prednisone) to less than 7.5 mg/day; and number of swollen jointsand/or number of joints with tenderness ≥3. Standard treatment regimen is defined asthe stable use of any of the following (alone or in combination): corticosteroids,nonsteroidal anti-inflammatory drugs ( NSAIDs) and csDMARDs, including methotrexate,leflunomide, hydroxychloroquine, salazosulfapyridine, elamodex, tretinoin, andpaeonia lactiflora total, as well as biological agents (including TNF inhibitors,non-TNF inhibitors, and JAK inhibitors).

3. Stable treatment with 1 or 2 cs DMARD(s) prior to enrollment as follows: at least 12weeks of methotrexate and at least 4 weeks of administration at a dose of 7.5-25mg/week; at least 4 weeks of stable hydroxychloroquine doses of ≤400 mg/d; at least 4 weeks of stable oral salicylazosulfapyridine 1 to 3 g/d; at least 4 weeks ofstable oral leflunomide 10-20 mg /d.

Patients with SLE will also be required to meet the following enrollment criteria:

1. Diagnosis of SLE according to the 2019 EULAR/ACR classification criteria for SLE.

2. A history of SLE for at least 6 months prior to screening, with the diseaseremaining active 2 months after the use of a standard treatment regimen prior toscreening. Standard treatment regimen is defined as stable use of any of thefollowing (alone or in combination): corticosteroids, antimalarials, nonsteroidalanti-inflammatory drugs (NSAIDs), and other immunosuppressive or biologic agents,including azathioprine, mertiomaxolide, cyclophosphamide, methotrexate, leflunomide,tacrolimus, cyclosporine, belimumab, rituximab, and tetracycline.

3. BILAG-2004 assessment of the presence of at least 1 grade A or 2 grade B organscores.

4. Positive for at least one of the following antibodies: anti-nuclear antibody,anti-ds-DNA antibody, anti-Sm antibody.

5. SLEDAI-2000 score ≥ 8 during the screening period.

Patients with dry syndrome were also required to meet the following enrollment criteria:

1. Diagnosis of dry syndrome according to the 2002 International ClassificationCriteria for Primary Dry Syndrome or the 2016 ACR/EULAR classification criteria.

2. Diagnosis of pSS-TP with platelet count <30 x 10^9/L.

3. History of dry syndrome for at least 6 months prior to screening and disease stillactive 2 months after use of conventional treatment regimen prior to screening.Definition of conventional therapy:Use of glucocorticoids (above 1 mg/Kg/d) andcyclophosphamide, and any of the following immunomodulatory drugs for more than 6months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate,leflunomide, tacrolimus, and cyclosporine, as well as biologics, such as rituximab,belimumab, and tetraciprazole.

Patients with systemic sclerosis were also required to meet the following enrollment criteria:

1. Diagnosis of systemic sclerosis according to the 2013 ACR classification criteriafor systemic sclerosis.

2. Positive antinuclear antibodies at screening.

3. Presence of clear evidence of HRCT progression.

4. History of systemic sclerosis for at least 6 months prior to screening, and activedisease 2 months after use of a conventional treatment regimen prior to screening.Definition of conventional therapy:Use of glucocorticoids (above 0.5 mg/Kg/d) andcyclophosphamide for more than 6 months, as well as any of the followingimmunomodulatory medications: antimalarials, azathioprine, mycophenolate mofetil,methotrexate, leflunomide, tacrolimus, and cyclosporine, as well as biologics, suchas rituximab and belimumab.

Exclusion Criteria:

1. pre-screening presence of clinically significant CNS disease or pathological changesnot caused by the disease itself, including, but not limited to: stroke, apoplexy,aneurysm, epilepsy, convulsions, aphasia, severe craniocerebral injury, dementia,Parkinson's disease, cerebellar disorders, organic brain syndromes, or insanity.

2. Those suffering from relatively serious heart diseases such as angina pectoris,myocardial infarction, heart failure and arrhythmia.

3. History of major organ transplantation or hematopoietic stem cell/bone marrowtransplantation.

4. vaccination, B-cell targeted therapy within 4 weeks prior to screening.

5. History of any malignant disease.

6. Patients with end-stage renal failure.

7. Presence or suspected presence of uncontrolled fungal, bacterial, viral or otherinfections.

8. History of severe allergy to drugs used in clinical studies or raw materials of testdrugs, such as cyclophosphamide, fludarabine, DMSO.

9. The patient is positive for HBV surface antigen, or HBV core antibody and positivefor DNA by RT-PCR; positive for HCV antibody or positive for HIV antibody orpositive for syphilis or positive for CMV DNA or positive for EBV DNA.

10. Females who are pregnant or breastfeeding or who plan to have a pregnancy within 2years of return infusion of the test drug; partners of male patients who plan tobecome pregnant within 2 years of treatment with the test drug.

11. Evidence of active tuberculosis infection.

12. other circumstances assessed by the investigator as unsuitable for enrollment.