A Study on the Safety, Preliminary Efficacy, and Cellular Kinetics of Allo-CD7 CAR-T Cells in T1DM

Inclusion criteria

• Patients with type 1 diabetes presenting with any of the following conditions:

Impaired hypoglycemia awareness (lack of sufficient autonomic symptoms when plasma glucose is below 54 mg/dL [3 mmol/L]) or other clinically diagnosed neuropathy caused by type 1 diabetes, including but not limited to gastrointestinal autonomic neuropathy Metabolic instability: two or more previous severe hypoglycemic events that required assistance from others, or two or more hospitalizations for ketoacidosis in the past year

• Age ≤ 60 years
• Body weight ≥ 40 kg
• At least one positive islet autoantibody, including glutamic acid decarboxylase autoantibody (GADA), protein tyrosine phosphatase autoantibody (IA-2A), insulin autoantibody (IAA) (only applicable within 2 weeks of insulin treatment), zinc transporter 8 antibody (ZnT8), islet cell autoantibody (ICA), etc.
• MMTT stimulated C-peptide peak > 0.1 nmol/L, or fasting C-peptide > 0.05 nmol/L
• Female subjects of childbearing potential must have a negative serum or urine pregnancy test at screening
• Both male and female subjects must be willing to use contraception from the time of signing the informed consent form until 12 months after cell infusion
• The subject or their legal guardian voluntarily participates in this study and is able to sign the informed consent form

Exclusion criteria

• If any of the following criteria are met, the subject will be excluded from the study.

Type 2 diabetes, or diabetes mellitus from pregnancy, single-gene mutation, pancreatic injury, or other secondary causes (e.g., Cushing's syndrome, thyroid dysfunction, or acromegaly)

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 x ULN, or total bilirubin ≥ 1.5 x ULN
• Severe heart disease, with any of the following:
• Myocardial infarction within 1 year before enrollment
• Signs or symptoms of heart failure of NYHA Class ≥ 3 within 1 year before enrollment
• Left ventricular ejection fraction (LVEF) < 50% at screening
• QTcF > 450 msec (males) or > 470 msec (females), based on the QTcF value from a single ECG or the average of three repeated ECGs taken more than 3 minutes apart (QT interval corrected by Fridericia's formula)
• Severe concurrent diabetic nephropathy, with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2
• Currently undergoing or expected to require renal replacement therapy during the study
• At screening, a subject tests positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B e-antigen (HBeAg); a subject tests positive for hepatitis B e-antibody (HBeAb) with a peripheral blood HBV DNA level above the upper limit of normal; a subject tests positive for hepatitis C virus (HCV) antibody; a subject tests positive for human immunodeficiency virus (HIV) antibody; a subject tests positive for syphilis antibody; a subject tests positive for EBER or has an EBV viral load greater than the upper limit of normal
• Participated in another clinical study within 3 months prior to enrollment
• Received a live attenuated vaccine within 4 weeks prior to enrollment
• The investigator considers the patient to have latent T1DM, including latent autoimmune diabetes in adults (LADA) and latent autoimmune diabetes in the young (LADY)
• The investigator believes there are other reasons that make the subject unsuitable for this clinical study