Anti-CD19 IL-10/IL15 CAR-NK Cells in Refractory/Relapsed Autoimmune Diseases

Common inlcusion Criteria: 1. Age 18-65 years old, male or female; 2. Routine blood count: hemoglobin ≥60g/L, white blood cell count ≥ 2.5×109/L, neutrophil count ≥1.0×109/L (no colony-stimulating factor treatment within 2 weeks before examination); 3. Liver function: ALT ≤3×ULN, AST≤3×ULN, TBIL≤1.5×ULN; 4. Coagulation function: international normalized ratio (INR) \< 1.5×ULN, prothrombin time (PT) \<1.5×ULN; 5. Cardiac function: good hemodynamic stability; 6. Female subjects of childbearing age must have a negative pregnancy test and agree to use effective contraception during the trial; 7. Voluntarily participate in this study and sign the informed consent form, agreeing to participate in the follow-up as required. SLE Enrollment Criteria: 1. patients meet the classification criteria of SLE; 2. Refractory or relapsed cases classified as non-response to standard therapy or disease recurrence after remission. Standard treatment is defined as therapy with at least three agents, including glucocorticoids at a dose \>1 mg/kg/day, together with at least two of the following immunomodulatory drugs administered for more than 6 months: cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, leflunomide, tacrolimus, cyclosporine, iguratimod, antimalarials, and biologic agents, including rituximab, belimumab, or telitacicept. Systemic Sclerosis (SSc) Enrollment Criteria: 1. Patients who meet the SSc classification criteria of the 2013 ACR/EULAR and have a diagnosis of systemic sclerosis; 2. the patient\'s disease duration ≤ 60 months (defined as the onset of the first non-Raynaud\'s symptoms); 3. Patient-modified Rodnan skin score (mRSS) ≥10 at the baseline visit; or active interstitial lung disease (ILD): ground-glass opacity on high-resolution computed tomography (HRCT), pulmonary function suggestive of forced vital capacity (FVC) or diffusing capacity for carbon monoxide (DLCO) less than 70% predicted; 4. A or B needs to be met: A. Refractory or relapsed cases classified as non-response to standard therapy or disease recurrence after remission. Standard treatment is defined as the use of glucocorticoids and cyclophosphamide, as well as any of the following immunomodulatory drugs, for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, tocilizumab, etc.; B. Presence of progressive disease, specifically defined as, within the past 6 months: a) Progression of cutaneous involvement: more than 25% increase in mRSS; or b) progression of lung disease: 10% reduction in FVC, or 5% reduction in FVC with 15% reduction in DLCO. Idiopathic Inflammatory myopathy enrollment criteria: 1. Diagnosis according to the 2017 EULAR/ACR classification criteria for inflammatory myopathies, including dermatomyositis (DM), polymyositis (PM), antisynthetase antibody syndrome (ASS), and immune-mediated necrotizing myositis (IMNM); 2. patients with muscle involvement with a manual strength test-8 (MMT-8) score less than 142 and at least 2 abnormalities in the following 5 core assessments: Physician Global Assessment (PhGA), Patient Global Assessment (PtGA), Extramuscular Disease Activity Score ≥2 points, Health Assessment Questionnaire (HAQ) total score ≥0.25, muscle enzyme level ≥1.5×ULN); or MMT-8≥142 with active interstitial lung disease (HRCT suggests ground-glass opacities); 3. Positive myositis-specific antibodies; 4. A or B needs to be met: A. Relapsed or refractory patients: relapsed or reactive after remission. Definition of conventional treatment: use of glucocorticoids (more than 1 mg/kg/d) and cyclophosphamide and any one or more of the following immunomodulatory drugs for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, tetatercept, etc.; B. Patients with progressive disease: rapid progressive interstitial pneumonia in a short period of time. ANCA-associated vasculitis enrollment criteria: 1. Meets the 2022 ACR/EULAR ANCA-ASSOCIATED VASCULITIS CLASSIFICATION CRITERIA, INCLUDING MICROSCOPIC POLYANGIITIS (MPA), GRANULOMATOSIS WITH POLYANGIITIS (MPA); 2. Positive PR3-ANCA or MPO-ANCA (either previous or current positive); 3. Birmingham Vasculitis Activity Scale (BVAS) score of ≥ 15 points, and at least 1 major item caused by active vasculitis, or at least 3 non-major items, or at least renal involvement hematuria, proteinuria; 4. estimated glomerular filtration rate (eGFR) ≥15 mL/minute/1.73 m2 (MDRD method); 5. Definition of refractory/relapsed: Conventional treatment that remains ineffective for more than 6 months, or disease recurrence after remission. Conventional treatment definition: use of glucocorticoids (more than 1 mg/kg/day) and cyclophosphamide, as well as any one or more of the following immunomodulatory drugs: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, tocilizumab, etc. Sjögren\'s syndrome enrollment criteria: 1. Meet the 2002 European and American Consensus Group (AECG) standards or the 2016 ACR/EULAR Primary Sjögren\'s Syndrome (pSS) classification criteria; 2. positive anti-SSA/Ro-60 antibody; 3. Definition of disease activity: EULAR Sjögren\'s Syndrome Disease Activity Index (ESSDAI) score ≥ 5; 4. Definition of recurrence/refractory: Conventional treatment that remains ineffective for more than 6 months, or disease recurrence after remission. Conventional treatment is defined as the use of glucocorticoids (\>1 mg/kg/day) and cyclophosphamide, as well as any one or more of the following immunomodulatory drugs: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including belimumab, rituximab, and tocilizumab. Antiphospholipid syndrom