Treatment for relapsed B cell lymphoma using CAR-NK and CAR-T cells

Inclusion Criteria:

1. Age 18-75 years old, no gender limit;
2. Histologically diagnosed as diffuse large B-cell lymphoma (DLBCL), transforming follicular lymphoma (TFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL) and other inert B-cells NHL conversion type:

   1. Refractory or relapsed DLBCL refers to the failure to achieve complete remission after 2-line treatment; disease progression during any treatment, or disease stable time equal to or less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation ；
   2. Refractory or relapsed MCL must be resistant to or intolerable to BTK inhibitors;
   3. Refractory or relapsed indolent B-cell NHL is the failure or recurrence of third-line treatment;
3. Previous treatment must include CD20 monoclonal antibody treatment (unless the subject is CD20 negative) and anthracyclines;
4. At least one measurable lesion with the longest diameter ≥ 1.5 cm exists;
5. The expected survival period is ≥12 weeks;
6. The puncture section of the tumor tissue was positive for CD19 expression;
7. ECOG score 0-2 points;
8. Sufficient organ function reserve:

   1. Alanine aminotransferase, aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value);
   2. Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min;
   3. Serum total bilirubin and alkaline phosphatase ≤1.5× UNL;
   4. Glomerular filtration rate\>50Ml/min
   5. Cardiac ejection fraction (EF) ≥50%;
   6. Under natural indoor air environment, basic oxygen saturation\>92%
9. Allow a previous stem cell transplantation
10. The approved anti-B-cell lymphoma treatments, such as systemic chemotherapy, systemic radiotherapy, and immunotherapy, have been completed for at least 3 weeks before the study medication;
11. Allow patients who have previously received CAR-T cell therapy and have failed or relapsed after 3 months of evaluation;
12. Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial
13. Two tests for the new coronavirus or swine flu virus are negative.

Exclusion Criteria:

1. Allergic to any of the components of cell products;
2. History of other tumors;
3. Acute GvHD or extensive chronic GvHD with grade II-IV (Glucksberg standard) in the past or are receiving anti-GVHD treatment;
4. Had received gene therapy within the past 3 months;
5. Active infections requiring treatment (except for simple urinary tract infections, bacterial pharyngitis); however, prophylactic antibiotics, antiviral and antifungal infection treatment are permitted;
6. Patents 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 dysfunction according to the New York Heart Association\'s cardiac function grading criteria;
8. Patients who received antitumor therapy earlier but did not recover from the toxicity (CTCAE 5.0 toxicity did not recover to ≤ grade 1, except fatigue, anorexia, alopecia);
9. Subjects with a history of epilepsy or other central nervous system disorders;
10. Head-enhanced CT or MRI showing evidence of central nervous system lymphoma;
11. Lactating women who are unwilling to stop breastfeeding;
12. Any other factors that the investigator believes may increase the risk to the subject or interfere with the test results.