Phase 1 Study of HBI0101 CAR-T in Refractory B-Cell Autoimmune Diseases

Inclusion Criteria: 1. Age: 18\~80 years old; for patients aged ≥ 75 years, geriatric assessment and endorsement are required; 2. Diagnosis of B-cell mediated ARDs listed below: SLE patients: individuals diagnosed with SLE according to American College of Rheumatology (ACR) and/or Systemic lupus international collaborating clinics (SLICC) classification criteria, who have severe and progressive disease course reflected by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score of 8 or more. Eligible patients must have failed to at least one of the conventional DMARDs (azathioprine, methotrexate, mycophenolate mofetil or cyclophosphamide), one of the calcineurin inhibitors (tacrolimus or cyclosporin) and one of the biologic agents (belimumab, rituximab or aniflorumab), each administered for a minimum of 3 months, or have a contraindication to, or have experienced toxicity from, any therapy within these categories. The failure is defined as: * lack of response per SLEDAI-2k (\<4 points reduction from baseline) or no improvement in BILAG domains, or * disease flare per SLEDAI-2k (≥4 points increase from baseline) or new BILAG A or ≥2 new BILAG B organ scores, or intolerance or discontinuation due to adverse effects. SSc patients: Patients who were diagnosed with diffuse or limited cutaneous SSc according to the College of Rheumatology/European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria, with severe or rapidly progressive disease Eligible patients must meet any of the following criteria: * Progression of skin thickening ≥ 12 over the past 6 months or Modified Rodnan skin score (mRSS) ≥15 * Any Medsger Disease Severity Score grade 3-4 in one major organ or grade ≥2 in two organs * Progressive interstitial lung disease evidenced by HRCT or FVC \<80% or DLCO \<80%, or evidence of pulmonary function decline, defined as an absolute FVC decline of ≥ 10% , or FVC decline of 5% -9% combined with DLCO 15%. * Other internal organ involvement. Eligible patients must have failed to at least two state-of-the-art immunosuppressive therapies including MTX, MMF, cyclophosphamide, azathioprine, nintedanib, tocilizumab or rituximab; each therapy must have been administered for a minimum of 3 months, unless discontinued due to a contraindication or toxicity. The failure is defined as: * lack of response in skin per mRSS (≤20% relative and ≤5 point absolute reduction from baseline) or no clinically meaningful improvement in FVC, DLCO, or other organ involved assessed by Medsger DSS, or * disease flare in skin per mRSS (increase in mRSS ≥20% and ≥5 points from baseline) or decline in FVC ≥10% predicted or in DLCO ≥15% predicted from baseline, other major SSc complication, or * intolerance or discontinuation due to adverse effects IIM, including dermatomyositis, anti-synthetase syndrome, immune mediated necrotizing myopathy, and polymyositis: patients must be diagnosed with IIM according to the 2017 ACR/EULAR Classification Criteria for idiopathic inflammatory myopathies. Eligible patients must have active disease, defined by at least one of the following: * CPK ≥4xULN * Loss of muscle strength in the weakest muscle group for less than 80% per MMT8 * Evidence on MRI of active myositis within last 6 months * Evidence on EMG of active myositis within last 6 months * Muscle biopsy evidence of active myositis within last 6 months Only patients with refractory disease will be recruited, defined as previous failure to (1) at least two of five non-glucocorticoids immunosuppressive therapies and (2) either rituximab or IVIG, each administered for a minimum of 3 months, or have a contraindication to, or have experienced toxicity from, any therapy within these categories. The five non-glucocorticoids therapies considered are azathioprine, MTX, MMF, IVIG, and rituximab The failure is defined as: * lack of response in muscle strength per MMT-8 or CPK (\<20% relative improvement) or per MRI or * disease flare in muscle strength per MMT-8 (≥30% decline) or CPK (≥30% rise) or objective worsening of other organ involvement per Myositis Disease Activity Assessment Tool or * intolerance or discontinuation due to adverse effects RA patients: Seropositive RA patients (positive for anti-cyclic citrullinated peptide and rheumatoid factor), diagnosed according to the 2010 ACR/EULAR classification criteria. Eligible patients must exhibit high disease activity (DAS28CRP ≥5.1), and be resistant to at least four conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARD) groups. Each patient must have previously received at least one medication from each of the mentioned groups, including * JAK-STAT inhibitors * Anti-TNF agents * Anti-IL6 drugs * Anti-CTLA4-Ig treatments, each administered for a minimum of 3 months, or have a contraindication to, or have experienced toxicity from, any therapy within these categories Drug resistance is defined as: * Inadequate clinical response measured by composite score DAS28CRP (\> 3.6) or failure to reach ACR20 or * Disease progression measured by DAS28CRP (≥20% increase) or radiographic progression or * Intolerance or discontinuation due to adverse effects NMOSD: Patients must be diagnosis of AQP4-IgG-positive NMOSD based on the 2015 International Panel for NMOSD Diagnosis (IPND) criteria (Wingerchuk et al., 2015). Eligible patients must have experienced at least two relapses in the past 24 months, with at least one occurring in the preceding 12 months before screening Each patients must have previously received with inadequate disease control (one or more clinical attacks, with new MRI activity, despite adequate treatment dosing) at least one immunosuppressant for at least 6 months (azathioprine or mycophenolate mofetil) and/or Rituximab for at least 3 months and/or a targeted therapy (eculizumab, inebilizum