Allogeneic Anti-CD19/BCMA CAR-T for Refractory Graves' Disease

Inclusion Criteria (Participants must meet all of the following inclusion criteria to be eligible for this study):

• Refractory Graves' disease, defined as meeting at least one of the following: a) Continuous treatment with antithyroid drugs (ATDs) for ≥3 years without achieving criteria for drug discontinuation. b) Meeting criteria for drug discontinuation but experiencing ≥2 relapses after withdrawal.

• Positive serum TRAb.

• Willing to voluntarily participate in this clinical study, able to sign informed consent, and compliant with follow-up requirements.

Exclusion Criteria (Participants will be excluded if any of the following conditions apply):

• History of severe drug allergies or allergic constitution.

• Presence or suspected presence of uncontrolled or active infections (including bacterial, fungal, viral, or other pathogens) requiring systemic or intravenous treatment.

• Presence of central nervous system disorders (including epilepsy, psychosis, cerebrovascular accident, encephalitis, CNS vasculitis, etc).

• Presence of clinically significant heart diseases (e.g., angina pectoris, myocardial infarction, heart failure, severe arrhythmias, etc).

• Subjects with congenital immunoglobulin deficiency.

• Subjects with malignancy (current or past), except for conditions deemed cured and with no risk of recurrence based on investigator assessment.

• Positive viral serology, including any of the following: Hepatitis B surface antigen (HBsAg)-positive, or hepatitis B core antibody (HBcAb)-positive with HBV DNA above the upper limit; Hepatitis C virus (HCV) antibody-positive with detectable HCV RNA; Human immunodeficiency virus (HIV) antibody-positive; Positive syphilis test.

• Severe psychiatric disorder or significant cognitive impairment that may affect compliance.

• Hematologic dysfunction, including: a) White blood cell count < 3.5 × 10⁹/L; b) Neutrophil count < 1.8 × 10⁹/L; c) Hemoglobin < 110 g/L.

• Hepatic dysfunction, defined as any of the following: Alanine aminotransferase (ALT) > 3 × ULN; Aspartate aminotransferase (AST) > 3 × ULN; Total bilirubin (TBIL) > 2.5 × ULN.

• Renal dysfunction: creatinine clearance rate (CrCl) < 60 mL/min (Cockcroft-Gault formula).

• Left ventricular ejection fraction (LVEF) < 55%.

• Coagulation abnormalities, defined as either: International normalized ratio (INR) > 1.5 × ULN; Prothrombin time (PT) > 1.5 × ULN.

• Participation in another clinical trial within 3 months prior to enrollment.

• Pregnant or breastfeeding women, or women planning to become pregnant.

• Any other condition that, in the opinion of the investigator, would make the participant unsuitable for the study.