Allogeneic Anti-CD7 CAR-T for Type 1 Diabetes

Inclusion criteria

• Age ≥18 years and ≤40 years.
• Participants with stage 2 or stage 3 type 1 diabetes mellitus, according to the staging criteria for type 1 diabetes defined in the ADA 2024 Standards of Care in Diabetes.
• Positive for at least one islet autoantibody at screening, including glutamic acid decarboxylase autoantibody (GADA), insulinoma-associated protein 2 autoantibody (IA-2A), insulin autoantibody (IAA) (applicable only to participants who have received insulin therapy for no more than 2 weeks), zinc transporter 8 autoantibody (ZnT8A), or islet cell autoantibody (ICA). Participants positive for two or more autoantibodies will be prioritized for enrollment.
• Peak C-peptide >0.2 nmol/L during a mixed-meal tolerance test (MMTT), or fasting C-peptide >0.1 nmol/L.
• The participant or his/her legally authorized representative voluntarily agrees to participate in the study and is able to sign the informed consent form.

Exclusion criteria

• Any type of diabetes other than type 1 diabetes, such as gestational diabetes, monogenic diabetes, diabetes caused by pancreatic injury, or other secondary forms of diabetes (for example, diabetes caused by Cushing syndrome, thyroid dysfunction, or acromegaly).
• Hematologic abnormalities at screening, including hemoglobin <100 g/L, white blood cell count <3 × 10^9/L, neutrophil count <1.5 × 10^9/L, or platelet count <75 × 10^9/L.
• Liver injury at screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 × the upper limit of normal (ULN), or total bilirubin ≥1.5 × ULN.
• Severe heart disease, such as angina pectoris, myocardial infarction, heart failure, or clinically significant arrhythmia.
• kidney disease, including severe diabetic kidney disease, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m², current or expected receipt of renal replacement therapy.
• Ongoing use of medications that, in the investigator's judgment, may cause significant and sustained changes in the course of type 1 diabetes or immune status.
• Uncontrolled diabetic ketoacidosis.
• Uncontrolled infection at screening, or any of the following at screening: positive hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg); positive hepatitis B e antibody (HBeAb) with peripheral blood HBV DNA above the upper limit of normal; positive hepatitis C virus (HCV) antibody; positive human immunodeficiency virus (HIV) antibody; positive syphilis antibody; positive Epstein-Barr virus-encoded RNA (EBER), or EBV viral load above the upper limit of normal.
• Active autoimmune disease other than type 1 diabetes that requires systemic immunotherapy or is associated with organ dysfunction.
• Pregnant or breastfeeding women; participants planning to conceive within 1 year; or participants of childbearing potential who are unwilling to use effective contraception during the study.
• History of malignancy, except for cases considered by the investigator to be cured and at no risk of recurrence.
• Participation in another clinical study within 3 months before enrollment.
• Receipt of a live attenuated vaccine within 4 weeks before enrollment, or plan to receive a live attenuated vaccine during the study period.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for this study.