An Early Clinical Study Evaluating the Safety and Efficacy of AcNK-Sup003 Cell Injection in the Treatment of Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Inclusion Criteria:

1. Signed an informed consent form in writing and is able to comply with the visits and related procedures specified in the protocol.
2. Age ≥18 years old, with an expected survival of more than 3 months.
3. Confirmed by pathology to have CD20+ relapsed or refractory B-cell non-Hodgkin's lymphoma (according to the WHO 2016 lymphoma classification standards), including but not limited to diffuse large B-cell lymphoma, high-grade B-cell lymphoma, and grade 3b follicular lymphoma.
4. Relapsed or refractory disease, defined by one or more of the following:

   * Relapse, non-response, or progression after hematopoietic stem cell transplantation.
   * Disease stabilization but with a duration of ≤6 months after at least two cycles of second-line therapy (must have received CD20-targeted drugs \[excluding CD20-negative tumors\] and anthracycline drugs).
   * Disease progression or relapse after second-line therapy (must have received CD20-targeted drugs \[excluding CD20-negative tumors\] and anthracycline drugs).
5. ECOG performance status of 0-2.
6. Males with fertility potential and women of childbearing age must agree to use effective contraception from the time of signing the informed consent form until 6 months after the last administration of the study drug; women of childbearing age must have a negative pregnancy test at screening.
7. Lymphoma must have at least one measurable lesion according to the Lugano 2014 criteria, that is, lymph node lesions with a long diameter \>15 mm or extranodal lesions with a long diameter \>10 mm, and positive FDG-PET scan (5PS score of 4 or 5); lesions that have previously received radiotherapy are only considered measurable if there is clear evidence of radiographic disease progression after completion of radiotherapy.
8. Hematological parameters (within 7 days before testing without transfusion or hematopoietic growth factor treatment): Hemoglobin (Hb) ≥80 g/L, Absolute Neutrophil Count (ANC) ≥1×10\^9/L, Platelet Count (PLT) ≥50×10\^9/L.
9. Coagulation function: International Normalized Ratio (INR) ≤1.5×ULN, and Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN (subjects on prophylactic anticoagulant therapy must have an INR between 2.0-3.0).
10. Hepatic, renal, and pulmonary function must meet the following requirements:

    1. Serum creatinine ≤1.5×ULN, or creatinine clearance ≥50 mL/min (estimated by the Cockcroft-Gault formula).
    2. Total bilirubin ≤1.5×ULN (≤3×ULN for subjects with liver lesions or Gilbert's syndrome).
    3. ALT and AST ≤3×ULN (≤5×ULN for subjects with liver lesions).
    4. Under indoor ventilation conditions and without oxygen supplementation, blood oxygen saturation is ≥92%.

Exclusion Criteria:

1. Primary central nervous system lymphoma, or active central nervous system involvement or symptoms of central involvement.
2. Accompanying active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, immune thrombocytopenia, etc.), uncontrolled multi-cavity effusions; presence of grade 2-4 acute graft-versus-host disease (GVHD) or moderate to severe chronic GVHD within 4 weeks before screening.
3. Severe cardiovascular and cerebrovascular history, including but not limited to:

   * Serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, second- or third-degree atrioventricular block, etc.
   * Prolonged QT interval corrected by the Fridericia formula (QTcF), \>450 ms for males; \>470 ms for females.
   * Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurring within 6 months before screening.
   * Heart failure with a New York Heart Association (NYHA) functional classification of ≥II or left ventricular ejection fraction (LVEF) \<50%.
   * Clinically uncontrollable hypertension, with systolic blood pressure still ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg after standardized drug treatment.
4. Received autologous hematopoietic stem cell transplantation or other autologous cell therapy products within 3 months before lymphodepletion; received allogeneic hematopoietic stem cell transplantation or other allogeneic cell therapy products within 6 months before lymphodepletion; subjects who have undergone other organ transplants.
5. Received anti-tumor drug treatment or participated in other interventional clinical studies within 4 weeks before lymphodepletion or within 5 half-lives (whichever is shorter), including but not limited to chemotherapy drugs, small molecule targeted drugs, monoclonal antibodies, antibody-drug conjugates, etc.
6. Received live attenuated vaccine immunization or major surgery within 4 weeks before lymphodepletion, or subjects who require live attenuated vaccine immunization or major surgery during the study period.
7. Requires long-term (≥3 days) systemic corticosteroid treatment during the study period (dose ≥10 mg/day prednisone or equivalent corticosteroids), excluding inhaled or topical use; as determined by the investigator.
8. History of other malignant tumors (except for cervical carcinoma in situ, non-invasive basal cell or squamous cell skin cancer, or localized prostate cancer treated with radical therapy, and ductal carcinoma in situ after radical surgery) in the past or concurrently; suffering from severe diabetes or other severe underlying diseases.
9. Subjects with fungal, bacterial, viral, tuberculosis, or other infections requiring systemic anti-infective treatment within 14 days before lymphodepletion.
10. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with HBV DNA copies above the lower limit of detection; positive for hepatitis C virus (HCV) antibody with HCV RNA copies above the lower limit of detection; positive for human immunodeficiency virus (HIV) antibody; positive for syphilis spirochete antibody.
11. Has life-threatening hypersensitivity reactions or other intolerable conditions to the drugs used in the study, or severe allergic constitution.
12. Pregnant or breastfeeding women.
13. The investigator deems that the subject has other conditions that may affect compliance or is not suitable for participating in this study.