In Vivo CAR-T for Refractory Graves' Disease
Trial Parameters
Brief Summary
Graves' disease is an autoimmune thyroid disorder characterized by the production of autoantibodies against the thyroid-stimulating hormone receptor (TRAb), leading to excessive thyroid hormone secretion and systemic manifestations. A subset of patients develop refractory disease, failing to achieve durable remission despite prolonged antithyroid therapy. This study aims to evaluate the safety and efficacy of HN2301, an in vivo CAR-T therapy in which host T lymphocytes are engineered and transformed to functional CAR-T cells via CD8 antibody-coated LNP delivery of CD19 CAR-mRNA. Participants with refractory Graves' disease will receive three to five administrations of HN2301 and will be regularly monitored for changes in thyroid function, TRAb levels, clinical response, and treatment-related adverse events. The study will provide preliminary evidence on whether HN2301 can induce sustained remission of refractory Graves' disease.
Eligibility Criteria
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