Clinical Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma

To study the safety and efficacy of cord blood-derived CAR-NK cells targeting CD19/CD70 in patients with B-cell non-Hodgkin's lymphoma

Inclusion Criteria:Voluntarily participate in the study and sign the informed consent;Age 18-75, male and female;Histologically confirmed diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), and other inert B-cell NHL transforming types:(1)refractory or recurrent DLBCL and tFL must be approved by 2 line immune disease relapse after chemotherapy treatment; (2) refractory definition large B cell lymphoma (research SCHOLAR - 1 standard) : more than 4 courses first-line immune chemotherapy disease progression; The stable time of the disease is equal to or less than 6 months; Or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation; (3) refractory or recurrent MCL must be 1 line with immune chemotherapy; BTK inhibitors are resistant or intolerant as 2-line therapy; (4)always treatment must include CD20 single resistance (unless the subjects for CD20 negative) and anthracycline-based;4. There was at least one measurable lesion with the longest diameter ≥1.5 cm;5. Predicted survival ≥12 weeks;6. The expression of CD19 or CD70 in biopsy sections of tumor tissue was positive;7. ECOG score 0-2;8. Adequate reserve of organ functions:cereal third transaminase, aspartate aminotransferase 2.5 x or less UNL (upper limit of normal);creatinine clearance (Cockcroft - Gault method) or 60 mL/min.serum total bilirubin and alkaline phosphatase (1.5 x or less UNL.glomerular filtration rate > 50 mL/minheart ejection fraction (EF) 45% or higher;indoor natural air environment, basic oxygen saturation > 92%blood routine: neutrophils absolute number > 1000 cells/mm3, platelet count 45 x109, 8.0 g/dL hemoglobin;9. Allowed to have received a previous stem cell transplant10. Approved anti-B-cell lymphoma therapies, such as systemic chemotherapy, systemic radiotherapy and immunotherapy, had been completed for at least 3 weeks before the study. The eluting period of targeted drug regimens without chemotherapy was 2 weeks;11. Patients who had previously received CAR T cell therapy and failed to respond to a 3-month evaluation or relapsed were admitted;12. Female subjects of childbearing age must test negative for pregnancy and agree to use effective contraceptive methods during the trial13. Two tests have come back negative for COVID-19.Exclusion Criteria:Allergic to any of the components of cell products;History of other tumors;Acute GvHD or generalized chronic GvHD with grade II-IV (Glucksberg standard) after previous allogeneic hematopoietic stem cell transplantation; Or being treated with anti-GVHD;Had received gene therapy in the past 3 months;Active infections requiring treatment (other than simple urinary tract infections and bacterial pharyngitis), however, prophylactic antibiotics, antiviral and antifungal infections are allowed;Subjects infected with hepatitis B (HBsAg positive, but HBV-DNA<103 is not excluded) or hepatitis C virus (including virus carriers), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to HIV-infected persons;Subjects with Grade III or IV cardiac insufficiency according to the New York Heart Association Cardiac Function Grading criteria;Patients who received antitumor therapy in the early stage but the toxicity reaction did not recover (CTCAE 5.0 toxicity reaction did not recover to ≤ level 1, except fatigue, anorexia and alopecia);Subjects with a history of epilepsy or other central nervous system diseases;Skull enhanced CT or MRI showing evidence of central nervous system lymphoma;Lactating women who refuse to stop breastfeeding;Any other circumstances that the investigator believes may increase the subject's risk or interfere with the test results.