Clinical Study on Targeted CD19/BCMA CAR-T Therapy for Autoimmune Diseases

Inclusion Criteria:

1. The subjects voluntarily participated in the study and signed the informed consentform.

2. Age ≥18 years old and ≤70 years old, both sexes.

3. Organ function and laboratory tests:

4. Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN), total bilirubin (TBIL) ≤2×ULN (exceptGilbert's syndrome).

5. Renal function: creatinine ≤1.5×ULN or creatinine clearance ≥40 ml/min.

6. Blood routine: neutrophil count ≥1×109/L, hemoglobin ≥60g/L, platelet count ≥20×109/L, lymphocyte count >0.3×109/L.

7. Coagulation: international normalized ratio (INR) ≤ 1.5×ULN, or prothrombintime (PT) ≤ 1.5×ULN.

8. Oxygen saturation (SpO2) ≥92% at rest in room air.

9. Left ventricular ejection fraction (LVEF) ≥50% on echocardiography.

10. Negative serum or urine pregnancy test results in female subjects of childbearingpotential at screening.

11. Women of childbearing potential must agree to use a highly effective method ofcontraception for at least 28 days before initiation of elution and up to 12 monthsafter RD06-04 reinfusion. Men of childbearing potential had to agree to the use ofan effective barrier method of contraception from the initiation of lymphoidectomyuntil 12 months after reinfusion of RD06-04 and had to refrain from donating semenor sperm throughout the trial.

SLE Patient Inclusion Criteria:

1. A definitive diagnosis of SLE according to the 2019 European League AgainstRheumatism (EULAR) / American College of Rheumatology (ACR) classification criteriaor the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria.

2. Positive antinuclear antibodies (ANA) at screening, and/or positiveanti-double-stranded DNA (anti-dsDNA) antibodies, and/or positive anti-Smithantibodies.

3. A SLEDAI-2K score >6 at screening, and a 'clinical' SLEDAI-2K score ≥4.

SSc Patient Inclusion Criteria:

1. Diagnosed with SSc according to the 2013 ACR/EULAR classification criteria.

2. Diagnosed with diffuse cutaneous SSc at screening, with a disease duration ≤6 years.

AAV Patient Inclusion Criteria:

1. Meeting the diagnostic criteria for ANCA-associated vasculitis established by the 2022 ACR/EULAR, including Microscopic Polyangiitis (MPA), Granulomatosis withPolyangiitis (GPA), and Eosinophilic Granulomatosis with Polyangiitis (EGPA).

2. Positive testing for ANCA-associated antibodies 3 months before screening or atscreening (specifically, positive anti-myeloperoxidase antibodies, MPO-ANCA, orpositive anti-proteinase 3 antibodies, PR3-ANCA).

IIM Patients Inclusion Criteria:

1. Diagnosed with IIM according to the 2017 ACR/EULAR classification criteria (including probable or definite diagnosis, i.e., probability ≥55%), includingsubtypes such as Dermatomyositis (DM), Anti-Synthetase Syndrome (ASS), andImmune-Mediated Necrotizing Myopathy (IMNM).

2. Patients in the active phase, defined as those with at least 2 of the following sixcore set measures being abnormal: decreased muscle strength (MMT-8 <142), PhysicianGlobal Assessment (PhGA, 10cm VAS) ≥2cm, Patient Global Assessment (PtGA, 10cm VAS) ≥2cm, Extramuscular Disease Activity Total Score (assessed using the MDAAT scoringtool) ≥2cm, Health Assessment Questionnaire (HAQ) ≥0.25, and Creatine Kinase (CK)muscle enzyme levels ≥1.5×ULN

Sjögren's Syndrome (SS) Patient Inclusion Criteria:

1. Diagnosed with primary Sjögren's Syndrome according to the 2016 ACR/EULARclassification criteria.

2. Positive for anti-SSA/Ro antibodies detected 3 months before screening or atscreening.

3. A score of ≥5 on the European League Against Rheumatism Sjögren's Syndrome DiseaseActivity Index (ESSDAI) at screening.

Exclusion Criteria:

1. SLE Patients: Those with uncontrolled lupus crisis within the 8 weeks prior toscreening, including rapidly progressive lupus nephritis, severe neuropsychiatriclupus, severe hemolytic anemia, severe immune thrombocytopenia, agranulocytosis,severe cardiac damage, severe lupus pneumonia, severe lupus hepatitis, and severevasculitis, as assessed by the investigator as unsuitable to participate in thisstudy.

2. IIM Patients: Presence of severe rhabdomyolysis or CK levels ≥120×ULN at screening.

3. Patients with severe asthma or Chronic Obstructive Pulmonary Disease (COPD) areeligible. Patients with mild or moderate asthma or COPD who are receiving stabletreatment can also be enrolled.

4. There has been an active infection requiring systemic treatment within 2 weeks priorto the urethral irrigation, such as infectious pneumonia, tuberculosis, etc.

5. Positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B coreantibody (HBcAb) with detectable hepatitis B virus (HBV) DNA in peripheral blood;positive for hepatitis C virus (HCV) antibody with detectable HCV RNA in peripheralblood; positive for human immunodeficiency virus (HIV) antibody; positive forsyphilis antibody.

6. Pregnant or breastfeeding women.

7. Any condition that, in the investigator's opinion, may affect study participation,pose a safety risk to the patient, or potentially confound the interpretation ofstudy results.