This is an exploratory, open-label, single-arm Phase 1 clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of QT-219C. QT-219C is a universal allogeneic chimeric antigen receptor T-cell (CAR-T) product targeting both CD19 and BCMA. The study targets subjects with refractory B-cell-related autoimmune diseases, including systemic lupus erythematosus (SLE), multi-drug resistant nephrotic syndrome (NS), IgA nephropathy (IgAN), systemic sclerosis (SSc), and ANCA-associated vasculitis (AAV) .The research is divided into two phases: a dose-escalation phase and a dose-expansion phase. Dose Escalation: Utilizes a standard "3+3" design to evaluate potential recommended dose(RD) and identify dose-limiting toxicities (DLTs) .Treatment Procedure: Eligible subjects will receive a lymphodepleting conditioning regimen followed by a single intravenous infusion of QT-219C .Primary Objectives: The primary goals are to evaluate the safety profile, including the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and to assess clinical response rates at 90 days post-infusion .Follow-up: Subjects will be monitored for pharmacokinetics (cell expansion), pharmacodynamics (B-cell depletion), and long-term safety for up to two years .
1)Bone Marrow Function: a. Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; b. Hemoglobin ≥ 60 g/L; c. Platelet count ≥ 30 × 10⁹/L.
2)Hepatic Function: ALT ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); AST ≤ 3 × ULN (except when elevation is attributable to inflammatory myopathy); Total bilirubin ≤ 2.0 × ULN (≤ 3.0 × ULN allowed for Gilbert syndrome).
3)Renal Function: eGFR ≥ 30 mL/min/1.73 m².(Participants with eGFR < 30 mL/min/1.73 m² and/or those receiving renal replacement therapy may be considered eligible if, in the investigator's judgment, the potential benefit outweighs the risk and the participant or guardian provides fully informed consent.)
4)Cardiac Function: Echocardiography shows no significant structural abnormalities and left ventricular ejection fraction (LVEF) ≥ 55%.
1. Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, tocilizumab), or subjects with a history of severe allergic reactions.
2.Subjects with grade III or IV heart failure (NYHA classification).
3.Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs.
4. Uncontrollable infection, or active infection that requires systemic treatment at screening.