An Exploratory Clinical Study of CD19 CAR NK Cells for the Treatment of Refractory Antisynthetase Antibody Syndrome and Rheumatoid Arthritis

Prior treatment

• Subjects who have received other clinical trial treatment within 3 months.

Other illness

• Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions.
• Subjects with one of the following genetic syndromes: Fanconi syndrome, Kostmann syndrome, Shwachman syndrome or any of the known bone marrow failure syndromes.
• Subjects with Active or uncontrolled infections requiring parenteral antimicrobials; evidence of severe active viral or bacterial infections or uncontrolled systemic fungal infections.
• Subjects with grade III or IV heart failure (NYHA classification).
• History of epilepsy or other central nervous system (CNS) diseases.
• Subjects with history of malignancy except cured of carcinoma in situ of the skin or cervix, and patients with inactive tumors.
• Subjects with pronounced bleeding tendencies, such as gastrointestinal bleeding, coagulation disorders, and hypersplenism.
• The subject with unstable angina, symptomatic congestive heart failure or myocardial infarction within the last 6 months.

Other

• Females who are pregnant, lactating, or planning a pregnancy within six months.

• Subjects voluntarily sign the Informed Consent Form (ICF) , participate in this clinical study and be willing to follow and be able to complete all trial procedures.
• Defined according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, adult patients with RA diagnosed ≥3 months prior to screening;Moderately to severely active RA;Poor response, or loss of response, or intolerance to at least one conventional synthetic DMARD (csDMARD) or biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD).
• Defined according to the 2020 ENMC-DM classification diagnostic criteria. Adult patients with ASyS diagnosed ≥3 months prior to screening; patients with moderately severe active ASyS.
• Age: ≥ 18 years old and ≤ 70 years old, male or female.
• Subjects with estimated survival \> 12 weeks.
• Serum creatinine clearance meets the relevant age/sex criteria, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN).
• ECOG score 0 - 2.
• The heart structure is essentially normal by echocardiography and Left ventricular ejection fraction (LVEF) ≥45%.
• 2 weeks after the subject received the last dose treatment (hormonal, immunosuppressive or other experimental treatment).