To study the safety and effectiveness of HLA haploidentical CAR-NK cells targeting CD19 in patients with B-cell non-Hodgkin's lymphoma

Inclusion Criteria:

1. Volunteer to participate in this study and sign an informed consent form;

2. Age 18-75 years old, no gender limit;

3. 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:

   • 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 ；
   • Refractory or relapsed MCL must be resistant to or intolerable to BTK inhibitors;
   • Refractory or relapsed indolent B-cell NHL is the failure or recurrence of third-line treatment;
   • 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:

   • Alanine aminotransferase, aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value);
   • Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min;
   • Serum total bilirubin and alkaline phosphatase ≤1.5× UNL;
   • Glomerular filtration rate>50Ml/min
   • Cardiac ejection fraction (EF) ≥50%;
   • 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 were negative.

Exclusion Criteria:

1. Those who have a history of allergies to any of the ingredients in cell products;

2. History of other tumors

3. Previously presented with II-IV degree (Glucksberg criteria) acute GvHD or extensive chronic GvHD; or are receiving anti-GvHD treatment;

4. Have received gene therapy in the past 3 months;

5. Active infections that require treatment (except for simple urinary tract infections and bacterial pharyngitis), but preventive antibiotics, antiviral and antifungal infection treatments are allowed;

6. Hepatitis B (HBsAg positive, but HBV-DNA <103 is not an exclusion criterion) or hepatitis C virus infection (including virus carriers), syphilis and other subjects with acquired and congenital immunodeficiency diseases, including But not limited to people living with HIV;

7. According to the New York Heart Association's Heart Function Classification Standard, it is classified as Grade III or Grade IV.

   Impaired subjects;

8. Those who have received anti-tumor therapy in the early stage but the toxic reaction has not recovered (the CTCAE 5.0 toxic reaction has not recovered to ≤1, except for fatigue, anorexia, and hair loss);

9. Subjects with a history of epilepsy or other central nervous system diseases;

10. Enhanced CT or MRI of the head showed evidence of central nervous system lymphoma;

11. Have received any other drugs that target CD19;

12. Women who are breastfeeding and unwilling to stop breastfeeding;

13. Any other situation that the investigator believes may increase the risk of the subject or interfere with the results of the test.