In vivo CAR-T treatment for refractory Graves' disease

A Safety and Efficacy Study of in Vivo CAR-T (HN2301) for Refractory Graves' Disease

This trial will test HN2301, an in‑body CAR‑T therapy, to see if it can control thyroid autoimmunity in adults whose Graves' disease has not responded to standard antithyroid drugs.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (Academic / other)
• Drugs / interventions: CAR-T
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07333677 on ClinicalTrials.gov

What this trial studies

This early phase 1 trial uses a CD8 antibody‑coated lipid nanoparticle to deliver CD19 CAR‑mRNA into the patient's own T cells in the body, converting them into functional CAR‑T cells. Eligible adults with refractory Graves' disease will receive three to five administrations of HN2301 and be followed closely for thyroid function, TRAb levels, clinical symptoms, and treatment‑related adverse events. The protocol emphasizes safety monitoring and preliminary signals of clinical remission or reduction in antibody levels. The single‑center study is conducted at Zhongshan Hospital, Fudan University in Shanghai.

Who should consider this trial

Good fit: Adults 18–75 years with refractory Graves' disease (longstanding antithyroid therapy without remission or ≥2 relapses after withdrawal) who are TRAb positive and willing to comply with follow‑up and contraception requirements are ideal candidates.

Not a fit: Patients with uncontrolled active infection, a history of major organ transplantation or severe allergic predisposition, pregnant people, or those with mild, easily controlled Graves' disease are unlikely to benefit from this experimental intervention.

Why it matters

Potential benefit: If successful, this approach could induce sustained remission of refractory Graves' disease and reduce the need for long‑term antithyroid drugs or definitive thyroid ablation.

How similar studies have performed: Autologous ex vivo CD19 CAR‑T treatments have shown promising case reports in some autoimmune diseases, but in‑body mRNA‑LNP delivery to generate CAR‑T cells is a novel approach and remains early and unproven for 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, 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.

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan Hospital Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Jingjing JIANG, MD, PhD

Conditions Graves' Disease; refractory Graves' disease; TSH receptor antibody; in vivo CAR-T