Safety and Efficacy Study of Anti-PD1 Armored CD19 CAR-T Cells in Adult Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

Inclusion Criteria

• •1\. Subjects voluntarily participate in clinical research and sign informed consent.
• •2\. Adult subjects (age ≥18 ) with relapsed or refractory diffuse large B-cell lymphoma: a) failure to achieve CR after 6 cycles, or PR after 3 cycles, of first-line therapy, or achieve CR after first-line therapy but relapse within 12 months; b) achieve CR after systemic treatment, but are refractory or relapsed, and no plan to transplant, or prepare for transplantation but cannot meet transplantation criteria after second-line therapy; c) not achieve CR after at least two courses of second-line treatment (including autologous stem cell transplantation).
• •3\. Expected survival ≥ 3 months.
• •4\. At least one measurable lesion as per revised IWG response criteria for malignant lymphom (2014 Lugano criteria).
• •5\. CD19 positive expression are detected on tumor cells of subjects by flow cytometry or immunohistochemistry.
• •6\. ECOG score ≤ 2.
• •7\. Subjects with adequate organ functions prior to enrollment, meet the following laboratory values:
• •Renal function: serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m².
• •Hepatic function: Serum alanine aminotransferase (ALT) ≤ 5 × age-specific ULN and total bilirubin ≤ 2.0 mg/dL, except in subjects with Gilbert-Meulengracht syndrome. If total bilirubin ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN, subjects with Gilbert-Meulengracht syndrome are included.
• •Pulmonary reserve: ≤ Grade 1 dyspnea and oxygen saturation \>95% on room air.
• •8\. Stable hemodynamics and left ventricular ejection fraction (LVEF) ≥ 45 % assessed by echocardiography or multi-gated radionuclide angiography (MUGA).
• •9\. Adequate bone-marrow reserve without blood transfusion as defined by:
• •Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L.
• •Absolute lymphocyte count (ALC) ≥ 0.1 x 10\^9/L.
• •Platelets ≥ 50 x 10\^9/L.
• •Hemoglobin \>80g/L.
• •10\. In the investigator's judgment, subjects' general condition and all biochemical values are either normal or sufficiently compensated to receive lymphodepletion and CAR-T cell therapy.