Safety and Efficacy of CD19 Targeted CAR-T Therapy for Refractory Autoimmune Disease

Inclusion Criteria26

• ≥18 years old, male or female;
• diagnosed with one of the following diseases:
• Systemic Lupus Erythematosus (SLE), EULAR/ACR 2019 standard;
• Sjogren's Syndrome (SS), 2016 ACR/EULAR standard;
• Systemic Scleroderma (SSc), 2013 ACR/EULAR Standards;
• Dermatomyositis (DM), 2017 EULAR/ACR classification standard + one positive myositis specific antibody (Jo-1, Zo, EJ, PL-7, KS, OJ, PL-12, YRS, Anti-NXP-2, Anti-TIF1g, Anti-Mi-2, Anti-SAE, Anti-MDA-5, Anti-SRP, Anti-HMGCR);
• Anti-neutrophil cytoplasmic antibody associated vasculitis (ANCA-AAV), including granulomatosis with polyangiitis (GPA), or microscopic vasculitis (MPA), or eosinophilic granulomatosis with polyangiitis (EGPA), 2022 ACR/EULAR standard.
• Disease activity meets the following requirements:
• SLEDAI score ≥8 for SLE patients;
• For SS patients, ESSDAI≥14 points;
• For patients with SSc, mRSS score in the range of 10-35 (including the boundary value) with interstitial pneumonia (ILD);
• Patients with DM who have been diagnosed for at least 1 year and meet the following conditions:
• \. Skin rash VAS score (based on MDAAT) ≥3cm with at least 3 abnormalities in CSM;
• , muscle biopsy pathology or muscle nuclear magnetic evidence of active inflammation;
• \. Bilateral manual muscle strength test (MMT-8) is less than 125/150, and at least 2 additional Core set measures (CSM) meet the following criteria: Patient score, 10 cm visual analogue scale (VAS) no less than 2.0 cm; b. Physician score, no less than 2.0 cm on the 10 cm VAS scale; c. Health Assessment Questionnaire (HAQ) disability index (Appendix 10) of not less than 0.25; d. Elevation of at least one muscular enzyme (including creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), with a minimum level of 1.3× the upper limit of normal; e. Disease activity score of extramuscular organs, no less than 1.0 cm on the 10 cm VAS scale (this VAS is the physician's comprehensive assessment of myositis disease Activity Assessment Tool (MDAAT) based on the general condition, skin, bone, gastrointestinal, lung, and heart scale activity score);
• For ANCA-AAV patients, the BVAS score was ≥15.
• ECOG 0\~1 score;
• The functions of important organs are basically normal:
• Hematology: hemoglobin ≥60g/L, platelet count ≥30×109/L;
• Cardiac function: Left ventricular ejection fraction (LVEF) ≥55%, no obvious abnormality in electrocardiogram;
• Renal function: eGFR≥30ML/min/1.73m2;
• Liver function: AST and ALT≤3.0 ULN, total bilirubin ≤2.0 ULN;
• Lung function: DLCO≥40% predicted value; FVC≥50% expected value;
• Have criteria for simple or intravenous blood collection, and no other contraindications for cell collection;
• The subject of childbearing age has a negative urine pregnancy test result and agrees to take effective contraceptive measures during the test period until 1 year after the infusion;
• The patient or his/her guardian agrees to participate in the clinical trial and signs the informed consent, indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.