In Vivo CAR-T for Refractory Graves' Disease

Inclusion criteria

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

• Age 18-75 years (inclusive), male or female.
• Refractory Graves' disease, defined as meeting at least one of the following: a) Continuous antithyroid drug (ATD) therapy for ≥3 years without achieving criteria for ATD discontinuation; b) Meeting criteria for ATD discontinuation but experiencing ≥2 relapses after ATD withdrawal.
• Positive serum TRAb.
• Willing to use effective contraception for 12 months after study drug administration.
• Voluntarily agrees to participate in the study, has signed the informed consent form, and is able to comply with study procedures and follow-up requirements.

Exclusion criteria

(Participants meeting any of the following criteria will be excluded from the study):

• History of severe drug allergy or known allergic predisposition.
• Presence or suspected presence of uncontrolled active infection.
• History of major organ transplantation (e.g., heart, lung, liver, kidney) or bone marrow/hematopoietic stem cell transplantation.
• Presence of significant heart disease, such as angina, myocardial infarction, heart failure, or clinically significant arrhythmias.
• Receipt of any mRNA-LNP product or other lipid nanoparticle (LNP)-based therapy within the past 2 years.
• Receipt of a live vaccine within 30 days prior to screening.
• History of malignant tumors.
• Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA above the detection limit; positive hepatitis C virus (HCV) antibody with detectable HCV RNA; positive human immunodeficiency virus (HIV) antibody; or positive syphilis test.
• Presence of psychiatric disorders or severe cognitive impairment.
• Hematologic dysfuction at screening, defined as any of the following: a. Neutrophil count < 1.8 × 10⁹/L, b. Hemoglobin < 110 g/L, c. Platelet count < 50 × 10⁹/L
• Impaired liver function, defined as any of the following: Alanine aminotransferase (ALT) > 3 × ULN, Aspartate aminotransferase (AST) > 3 × ULN, Total bilirubin > 2.5 × ULN.
• Impaired renal function: 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
• Pregnant or breastfeeding women.
• Any other condition that, in the opinion of the investigator, would make the participant unsuitable for the study.