CD19 CAR-T in the Treatment of Relapsed/Refractory Autoimmune Diseases

Inclusion Criteria: * 1、aged 18 to 65 years (including 18 and 65 years), male or female; * 2、Special criteria for different indications: * 2.1 Subjects with relapsed/refractory moderate to severe SLE must meet the following criteria: * 1\) diagnosis of SLE according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE; * 2\) positive antinuclear antibody (ANA) (titer ≥ 1:80), and/or positive anti-dsDNA -antibody, and/or positive anti-Sm antibody at screening; * 3\) moderate to severe activity is defined as: SLEDAI-2000 ≥ 8 points at screening; if there is a score of low complement and/or anti-dsDNA antibody, the score for clinical symptoms of SLEDAI-2000 (except low complement and/or anti-ds-DNA antibody) needs to be ≥ 6 points; * 4\) stable standard treatment regimen for at least 6 months in the history of SLE before screening, and the disease remains active for at least 2 months before screening. Standard treatment regimen refers to stable use of any of the following drugs (alone or in combination): glucocorticoids (≤ 20 mg/day prednisone or equivalent), antimalarials (hydroxychloroquine ≤ 400 mg/day, chloroquine ≤ 500 mg/day), non-steroidal anti-inflammatory drugs (NSAIDs), biologics (rituximab, belimumab, tatacept) and other immunosuppressive agents or immunomodulators, including mycophenolate mofetil (≤ 2 g/day), azathioprine (≤ 2 mg/kg/day), methotrexate (≤ 20 mg/week); * 2.2 Subjects with relapsed/refractory dcSSc were required to meet the following criteria: * 1\) diagnosis of SSc according to the 2013 EULAR/ACR classification criteria for systemic sclerosis (SSc); * 2\) diffuse cutaneous manifestations according to the 1988 LeRoy et al criteria, ie, extensive skin fibrosis with proximal elbow and/or knee skin involvement; * 3\) interstitial lung disease (ILD) at screening, and 45% predicted ≤ forced vital capacity (FVC) ≤ 70% predicted, or 40% predicted ≤ diffusing capacity for carbon monoxide (DLCO) ≤ 70% predicted; * 4\) relapse/refractory was defined as failure to respond to prior conventional therapy or relapse after disease remission. Conventional therapy was defined as the use of corticosteroids, cyclophosphamide, and at least 1 immunosuppressive/modifying agent for ≥ 6 months, including azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, rituximab, belimumab, and taitacept; * 5\) activity was defined as having at least 1 of the following: evidence of skin progression at screening, ie, an increase in mRSS score of ≥ 10% within the past 6 months; evidence of any of the following ILD activities at screening: newly diagnosed ILD within the past 6 months; decline in FVC of 10%, or decline in FVC of 5% with DLCO of 15% within the past 6 months in subjects with preexisting ILD. * 2.3 Subjects with/refractory AAV must meet the following criteria: * 1\) a clinical diagnosis of granulomatous vasculitis (GPA) and microscopic polyangiitis (MPA) as defined by the 2012 Chapel Hill Consensus Conference (CHCC); * 2\) at least one major item or at least three other items in Birmingham Vasculitis Activity Score (BVAS) version 3; * 3\) positive antiproteinase-3 (PR3-ANCA) antibody or antimyeloperoxidase (MPO-ANCA) antibody at screening; * 4\) relapsed/refractory as defined by: Subjects with relapsed AAV: initial response to prior treatment with corticosteroids combined with immunosuppressive agents (cyclophosphamide, rituximab, azathioprine, methotrexate, mycophenolate mofetil, etc.) for at least 3 months (BVAS score 0 and glucocorticoid dose ≤ 7.5 mg/day prednisone or other equivalent glucocorticoid agents) or 1 - 2 additional items emerging in two consecutive assessments),Patients with relapsed disease within 12 weeks before screening; subjects with refractory AAV: those who had not achieved response after at least 3 months of previous treatment with glucocorticoids combined with immunosuppressive agents (cyclophosphamide, rituximab, azathioprine, methotrexate, mycophenolate mofetil, etc.) (BVAS score of 0 and glucocorticoid dose ≤ 7.5 mg/d prednisone or other equivalent glucocorticoid drugs); * 2.4 Subjects with relapsed/refractory IIM were required to meet the following criteria: * 1\) have a ≥ 55% probability of being diagnosed with IIM according to the 2017 EULAR/ACR classification criteria for IIM, and were classified as having dermatomyositis (DM), polymyositis (PM), or immune-mediated necrotizing myopathy (IMNM) based on age at first onset, skin and muscle strength performance, laboratory tests, and muscle biopsy characteristics:； * 2\) disease activity/severity meeting the following criteria: free-hand muscle strength test-8 (MMT-8) score ≤ 141 (total score 150)；meet at least 2 of the other CSMs abnormalities: overall disease activity assessed by the patient \[based on visual analogue scale (VAS)\] score ≥ 2 points (range 0 - 10 points); overall disease activity VAS score ≥ 2 points (range 0 - 10 points) assessed by the physician; VAS score ≥ 2 points (range 0 - 10 points) for extramuscular overall disease activity assessed by the physician; Physician assessed health assessment questionnaire disability index (HAQ-DI) score ≥ 0.25 (range 0-3). At least 1 muscle enzyme level \> 1.5 times the upper limit of normal (ULN). * 2.5 Subjects with relapsed/refractory SS were required to meet the following criteria: * 1\) diagnosis of SS according to the 2016 EULAR/ACR classification criteria for SS; * 2\) anti-Ro/SSA antibody positivity at screening; * 3\) dynamic total salivary flow rate ≥ 0.05 mL/min or static total salivary flow rate ≥ 0.01 mL/min at screening; * 4\) activity was defined as: Sjögren 's Syndrome Disease Activity Index (ESSDAI) score ≥ 5 on 8 subitems; * 3\. The above autoimmune diseases that are intolerant to glucocorticoids and at least one other immunosuppressive agent or modulator or have insufficient efficacy in the past require: at least 3 months of treatme