Overview

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

Eligibility

Inclusion Criteria:

1. Voluntarily participate in the study and sign the informed consent;
2. Age 18-75, male and female;
3. 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:
          1. cereal third transaminase, aspartate aminotransferase 2.5 x or less UNL (upper limit
             of normal);
          2. creatinine clearance (Cockcroft - Gault method) or 60 mL/min.
          3. serum total bilirubin and alkaline phosphatase (1.5 x or less UNL.
          4. glomerular filtration rate > 50 mL/min
          5. heart ejection fraction (EF) 45% or higher;
          6. indoor natural air environment, basic oxygen saturation > 92%
          7. 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 transplant
        10. 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 trial
        13. Two tests have come back negative for COVID-19.
        Exclusion Criteria:
          1. Allergic to any of the components of cell products;
          2. History of other tumors;
          3. 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;
          4. Had received gene therapy in the past 3 months;
          5. Active infections requiring treatment (other than simple urinary tract infections and
             bacterial pharyngitis), however, prophylactic antibiotics, antiviral and antifungal
             infections are allowed;
          6. 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;
          7. Subjects with Grade III or IV cardiac insufficiency according to the New York Heart
             Association Cardiac Function Grading criteria;
          8. 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);
          9. Subjects with a history of epilepsy or other central nervous system diseases;
         10. Skull enhanced CT or MRI showing evidence of central nervous system lymphoma;
         11. Lactating women who refuse to stop breastfeeding;
         12. Any other circumstances that the investigator believes may increase the subject's risk
             or interfere with the test results.