Safety and Efficacy Study of CD19-CAR-DNT Cells in Autoimmune Diseases

Inclusion Criteria:

1. Voluntarily sign an ICF and expect to complete the study procedures for follow-upexaminations and treatment;
2. Aged 18 to 75 years (including cut-offs), regardless of gender;
3. Appropriate organ function, and accordance with the following criteria within 7 daysprior to lymphodepleting chemotherapy: Coagulation function: a) Fibrinogen ≥1.0 g/L; b) Activated partial thromboplastin time ≤1.5 times the upper limit of normal (ULN); c) Prothrombin time (PT) ≤1.5 times ULN; Liver function: a) Glutathione aminotransferase (AST) ≤ 3 times the upper limit ofnormal (ULN); b) Glutamic aminotransferase (ALT) ≤ 3 times ULN; c) Total bilirubin ≤ 1.5 times ULN, unless the subject has documented Gilbert syndrome. Subjects withGilbert-Meulengracht syndrome with total bilirubin ≤ 1.5 times ULN may be included; Renal function: serum creatinine ≤ 1.5 times ULN, or creatinine clearance ≥ 60 mL/min (see Appendix 2 for Cockcroft-Gault formula); Complete blood count: a) Hemoglobin ≥ 80 g/L or hemoglobin maintained at that levelfollowing transfusion; b) absolute neutrophil count (ANC) ≥ 1.0×10^9/L; c) A plateletcount ≥ 30 x 10^9/L or a platelet count maintained at that level following a platelettransfusion; Cardiopulmonary function: left ventricular ejection fraction (LVEF) ≥45%;
4. Female patients with of childbearing potential should have a negative pregnancy testduring the screening period. Any male and female patients of childbearing potentialmust agree to use an effective contraception method for at least six months from thetime that they sign the informed consent form until the end of the cell infusion.Female patients without childbearing potential (meeting at least 1 of the followingcriteria) is described below:
5. Have undergone a hysterectomy or bilateral oophorectomy;
6. Medically recognized as ovarian failure;
7. Medically recognized as post-menopausal (at least 12 consecutive months ofmenopause without pathological or physiological cause);
8. Meets the criteria of relapsed/refractory autoimmune diseases in 2022 EULAR/ACR.

Exclusion Criteria: 1. Individuals with a history of severe drug allergies or allergic constitution; 2. Active infectious diseases: such as tuberculosis, central nervous system infection,hepatitis, enteritis, etc.; 3. The following serious diseases: malignant tumor, end-stage renal failure, alveolarhemorrhage requiring mechanical ventilation, acute mononeuritis multiplex, or CNSinvolvement; 4. Renal disease: creatinine clearance rate < 60mL/min and serum creatinine > 1.5 timesULN within 1 week before lymphodepleting chemotherapy; Patients required hemodialysisor high-dose glucocorticoid therapy (e.g., prednisone (or equivalent) ≥100mg per day)within 6 months before screening; 5. Cardiovascular disease: unstable angina, cerebrovascular accident or transientischemic attack, myocardial infarction, New York Heart Association class III or IVcardiac dysfunction, or refractory hypertension within 6 months before screening (refractory hypertension was defined as: on the basis of lifestyle modification,patients were treated with adequate and reasonably tolerable doses of ≥3antihypertensive drugs (including diuretics) for > 1 month or with ≥4 antihypertensivedrugs for effective blood pressure control) and a history of severe arrhythmiarequiring drug treatment; 6. Other uncontrollable diseases: clinically unstable or not effectively controlledacute/chronic diseases unrelated to AID (such as acute pneumonia, diabeticketoacidosis, acute pancreatitis, etc.) that may confound study results or affectinvestigators' assessment of efficacy/safety; 7. Patients with positive hepatitis B surface antigen (HBsAg) or hepatitis B coreantibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titration assay notwithin the normal reference range, positive hepatitis C virus (HCV) antibody andperipheral blood HCV RNA, positive for human immunodeficiency virus (HIV), or positivefor cytomegalovirus (CMV) DNA, or positive syphilis test; 8. The presence of active or uncontrollable infections requiring systemic treatment (except simple urinary tract infections or upper respiratory tract infections) andcurrently receiving suppressive therapy for any chronic infection (e.g., tuberculosis,Pneumocystis carinii, cytomegalovirus, herpes simplex virus, herpes zoster, andatypical mycobacteria); 9. Vaccination with live or attenuated live vaccine within 1 month before screening; 10. Persons who have previously received an organ transplant or are preparing to receivean organ transplant; 11. Patients have received CAR-T therapy or other gene-modified cell therapy prior toenrolment; 12. Received rituximab treatment within 6 months prior to screening; Received belimumaband telitacicept within 30 days prior to initial administration of the investigationaldrug; JAK inhibitor discontinuation time is less than 5 half-lives; 13. Patients with a life expectancy of less than 3 months; 14. Patients have been involved in other clinical studies within 3 months prior toscreening; 15. Patients, in the judgement of the investigator and/or clinical criteria, arecontraindicated to any study procedure or have other medical conditions that may placethem at unacceptable risk.